{"id":46324,"date":"2025-01-13T05:12:18","date_gmt":"2025-01-13T05:12:18","guid":{"rendered":"https:\/\/zydq.1006ss.com\/?p=46324"},"modified":"2025-01-13T05:12:18","modified_gmt":"2025-01-13T05:12:18","slug":"gastroenterology-alkbh5-%e4%bf%83%e8%bf%9b%e7%bb%93%e7%9b%b4%e8%82%a0%e7%99%8cicb%e6%b2%bb%e7%96%97%e7%9a%84%e5%88%86%e5%ad%90%e9%9d%b6%e7%82%b9%ef%bc%8c%e9%9d%b6%e5%90%91axin2%e9%a9%b1%e5%8a%a8","status":"publish","type":"post","link":"http:\/\/zydq.1006ss.com\/?p=46324","title":{"rendered":"Gastroenterology | ALKBH5-\u4fc3\u8fdb\u7ed3\u76f4\u80a0\u764cICB\u6cbb\u7597\u7684\u5206\u5b50\u9776\u70b9\uff0c\u9776\u5411AXIN2\u9a71\u52a8\u514d\u75ab\u6291\u5236"},"content":{"rendered":"

\u7ed3\u76f4\u80a0\u764c\uff08CRC\uff09\u4e3a\u5e38\u89c1\u764c\u75c7\u4e4b\u4e00\uff0c\u7531\u4e8e\u80bf\u7624\u7684\u8f6c\u79fb\u548c\u590d\u53d1\uff0cCRC\u6b7b\u4ea1\u7387\u5c45\u9ad8\u4e0d\u4e0b\u3002\u7ed3\u76f4\u80a0\u764c\u7684\u53d1\u751f\u548c\u53d1\u5c55\u6d89\u53ca\u4e00\u7cfb\u5217\u7684\u57fa\u56e0\u548c\u8868\u89c2\u9057\u4f20\u6539\u53d8\uff0c\u8fd8\u53d7\u80bf\u7624\u514d\u75ab\u5fae\u73af\u5883\uff08TIME\uff09\u5f71\u54cd\u3002\u867d\u7136\u76ee\u524d\u7ed3\u76f4\u80a0\u764c\u7684\u5316\u7597\u548c\u514d\u75ab\u6cbb\u7597\u53d6\u5f97\u4e86\u5f88\u5927\u8fdb\u5c55\uff0c\u4f46\u60a3\u8005\u9884\u540e\u5e76\u4e0d\u7406\u60f3\u3002\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\uff08ICB\uff09\u6cbb\u7597\u4ec5\u5bf9\u4e00\u5c0f\u90e8\u5206\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u6709\u76ca\uff0c\u800c\u8bc6\u522bCRC\u5185\u5728\u4e8b\u4ef6\u8c03\u8282\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u7597\u6548\u7684\u9700\u6c42\u5c1a\u672a\u5f97\u5230\u6ee1\u8db3\u3002\u56e0\u6b64\uff0c\u4e3a\u4e86\u5f00\u53d1\u65b0\u7684\u6297\u7ed3\u76f4\u80a0\u764c\u514d\u75ab\u6cbb\u7597\u7b56\u7565\uff0c\u9700\u9610\u660e\u7ed3\u76f4\u80a0\u764c\u5185\u6e90\u6027\u4e8b\u4ef6\u4e0e\u5bbf\u4e3b\u514d\u75ab\u53cd\u5e94\u4e4b\u95f4\u7684\u4e32\u6270\u3002<\/p>\n

N6-\u7532\u57fa\u817a\u82f7\uff08m6<\/sup>A\uff09RNA\u4fee\u9970\u662f\u80bf\u7624\u751f\u7269\u5b66\u4e2d\u7684\u4e00\u79cd\u8868\u578b\u8c03\u63a7\u673a\u5236\uff0c\u4e3a\u4fe1\u4f7fRNA\uff08mRNA\uff09\u4e2d\u6700\u4e30\u5bcc\u7684\u4fee\u9970\uff0c\u8c03\u8282mRNA\u7684\u526a\u63a5\u3001\u964d\u89e3\u548c\u7ffb\u8bd1\u3002m6<\/sup>A\u4fee\u9970\u7531m6<\/sup>A writers\uff08\u7532\u57fa\u5316\u8f6c\u79fb\u9176\uff09Mettl3\/Mettl14\/WTAP\u548cm6<\/sup>A eraser \uff08\u53bb\u7532\u57fa\u5316\u9176\uff09AKBH5\/FTO\u52a8\u6001\u8c03\u8282\u3002m6<\/sup>A reader\uff08\u7ed3\u5408\u86cb\u767d\uff09\uff0c\u5982YTHDF1\/2\/3\u3001YTHDC1\/2\u548cIGF2BP1\/2\/3\uff0c\u53ef\u4ee5\u76f4\u63a5\u4e0em6<\/sup>A\u4fee\u9970\u7684mRNA\u7ed3\u5408\uff0c\u5bfc\u81f4mRNA\u526a\u63a5\u3001\u8f93\u51fa\u3001\u7a33\u5b9a\u6027\u548c\u7ffb\u8bd1\u7684\u6539\u53d8\u3002\u4f46\u76ee\u524dm6<\/sup>A\u4fee\u9970\u5bf9\u80bf\u7624\u514d\u75ab\u5fae\u73af\u5883 \uff08TIME\uff09\u7684\u6f5c\u5728\u5f71\u54cd\u4ecd\u4e0d\u6e05\u695a\u3002<\/p>\n

\u8fd1\u65e5\u6765\u81ea\u9999\u6e2f\u4e2d\u6587\u5927\u5b66\u4e8e\u541b\u56e2\u961f\u53d1\u73b0ALKBH\u540c\u6e90\u72695 \uff08ALKBH5\uff09\u80fd\u9a71\u52a8\u514d\u75ab\u6291\u5236\uff0c\u662f\u4fc3\u8fdb\u7ed3\u76f4\u80a0\u764c ICB \u6cbb\u7597\u7684\u5206\u5b50\u9776\u70b9\u3002\u8be5\u7814\u7a76\u4e8e2023\u5e745\u6708\u53d1\u8868\u4e8e\u6742\u5fd7\u300aGastroenterology\u300b\uff0c\u9898\u4e3a\u201cALKBH5 Drives Immune Suppression via targeting AXIN2 to Promote Colorectal Cancer and is a Target for Boosting Immunotherapy.\u201d<\/p>\n

\u56fe\u6e90\uff1a\u300aGastroenterology\u300b<\/p>\n

ALKBH5\u4e0e\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u9884\u540e\u4e0d\u826f\u76f8\u5173<\/p>\n

\u4e3a\u8bc4\u4ef7ALKBH5\u7684\u4e34\u5e8a\u610f\u4e49\uff0c\u4f5c\u8005\u5bf9205\u4f8b\u7ed3\u76f4\u80a0\u764c\u60a3\u8005ALKBH5\u86cb\u767d\u8868\u8fbe\u8fdb\u884c\u68c0\u6d4b\u3002Kaplan Meier\u66f2\u7ebf\u663e\u793aALKBH5\u86cb\u767d\u9ad8\u8868\u8fbe\u4e0e\u603b\u751f\u5b58\u7387\u5dee\u76f8\u5173\u3002\u5e94\u7528\u591a\u56e0\u7d20COX\u56de\u5f52\u5206\u6790ALKBH5\u7684\u8868\u8fbe\u4e0e\u6027\u522b\u3001\u5e74\u9f84\u3001\u80bf\u7624\u90e8\u4f4d\u3001TNM\u5206\u671f\u7b49\u5176\u4ed6\u5371\u9669\u56e0\u7d20\u5bf9\u7ed3\u76f4\u80a0\u764c\u9884\u540e\u7684\u5f71\u54cd\u3002\u7ed3\u679c\u8868\u660e\uff0cALKBH5\u86cb\u767d\u9ad8\u8868\u8fbe\u662f\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u9884\u540e\u4e0d\u826f\u7684\u72ec\u7acb\u56e0\u7d20\uff0c\u4e14ALKBH5\u7684mRNA\u9ad8\u8868\u8fbe\u9884\u793a\u7740\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u7684\u603b\u4f53\u751f\u5b58\u7387\u8f83\u4f4e\u3002\u591a\u53d8\u91cfCOX\u56de\u5f52\u5206\u6790\u8bc1\u5b9eALKBH5\u662f\u7ed3\u76f4\u80a0\u764c\u9884\u540e\u4e0d\u826f\u7684\u72ec\u7acb\u56e0\u7d20\uff08\u56fe1A\uff09\u3002<\/p>\n

ALKBH5\u7f3a\u5931<\/p>\n

\u8bf1\u5bfc\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u79fb\u690d\u7624\u6a21\u578b\u7684\u514d\u75ab\u6291\u5236<\/p>\n

\u4e3a\u4e86\u7814\u7a76ALKBH5\u4ecb\u5bfc\u7684m6<\/sup>A\u4fee\u9970\u662f\u5426\u8c03\u8282\u7ed3\u76f4\u80a0\u764c\u514d\u75ab\u5fae\u73af\u5883\uff0c\u4f5c\u8005\u6784\u5efa\u4e862\u4e2a\u7a33\u5b9a\u7684ALKBH5\u57fa\u56e0\u6572\u9664\u7684\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\uff08MC38\u548cCT26\uff09\u3002MTT\u6cd5\u8bc1\u5b9e\u6c89\u9ed8ALKBH5\u53ef\u6291\u5236MC38\u548cCT26\u7ec6\u80de\u7684\u4f53\u5916\u751f\u957f\uff08\u56fe1B\uff09\u3002\u6697\u793aALKBH5\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u7684\u8868\u8fbe\u53ef\u80fd\u8c03\u8282\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u3002<\/p>\n

\u63a5\u4e0b\u6765\uff0c\u7814\u7a76\u4eba\u5458\u901a\u8fc7\u591a\u8272\u6d41\u5f0f\u7ec6\u80de\u672f\u7814\u7a76ALKBH5\u662f\u5426\u6539\u53d8\u4e86\u5c0f\u9f20\u7684\u514d\u75ab\u7ec6\u80de\u7ec4\u6210\u3002\u5728MC38\u540c\u57fa\u56e0\u5c0f\u9f20\u6a21\u578b\u4e2d\uff0cALKBH5\u57fa\u56e0\u6572\u9664\u663e\u8457\u964d\u4f4e\u4e86\u80bf\u7624\u4f53\u79ef\u548c\u91cd\u91cf\uff08\u56fe1C\uff09\u3002\u5728ALKBH5\u7f3a\u9677\u7684\u80bf\u7624\u4e2d\u89c2\u5bdf\u5230\u663e\u8457\u51cf\u5c11\u7684\u9aa8\u9ad3\u6e90\u6027\u6291\u5236\u7ec6\u80de\uff08MDSCs\uff09\u6e17\u900f\uff0c\u5305\u62ec\u5355\u6838\u7ec6\u80deMDSCs\u548c\u7c92\u7ec6\u80deMDSCs\uff0c\u4ee5\u53ca\u589e\u52a0\u7684NK\u548cCD8+<\/sup>T\u7ec6\u80de\u7fa4\uff08\u56fe1D\uff09\u3002\u4e14\u5728CT26\u540c\u57fa\u56e0\u6a21\u578b\u4e2d\uff0cALKBH5\u7684\u7f3a\u5931\u663e\u8457\u6291\u5236\u4e86\u80bf\u7624\u7684\u751f\u957f\uff0c\u5e76\u589e\u5f3a\u4e86\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\uff08\u56fe1E\u548cF\uff09\u3002\u514d\u75ab\u8367\u5149\u67d3\u8272\u8bc1\u5b9eALKBH5\u7f3a\u5931\u7684MC38\u548cCT26\u80bf\u7624\u4e2dMDSCs\u7684\u6d78\u6da6\u51cf\u5c11\uff08\u56fe1G\uff09\u3002\u56e0\u6b64\uff0cALKBH5\u901a\u8fc7\u8c03\u8282MDSCs\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u7684\u6e17\u900f\u6765\u8c03\u8282\u514d\u75ab\u6291\u5236\u3002<\/p>\n

\u56fe1.ALKBH5\u9884\u6d4b\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u7684\u4e0d\u826f\u9884\u540e\uff0c\u5e76\u8c03\u8282\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u4e2d\u514d\u75ab\u7ec6\u80de\u7684\u6e17\u900f<\/p>\n

\u4eba\u7ed3\u76f4\u80a0\u764c\u7ec6\u80deALKBH5\u57fa\u56e0\u6572\u9664<\/p>\n

\u4fc3\u8fdbCD34\uff0b<\/sup>\u4eba\u6e90\u5316\u5c0f\u9f20\u7684\u6297\u80bf\u7624\u514d\u75ab<\/p>\n

\u63a5\u4e0b\u6765\uff0c\u4e3a\u4e86\u9a8c\u8bc1ALKBH5\u5bf9\u4eba\u7ed3\u76f4\u80a0\u764c\u7684\u514d\u75ab\u6291\u5236\u4f5c\u7528\uff0c\u4f5c\u8005\u6784\u5efa\u4e86CD34\uff0b<\/sup>\u4eba\u6e90\u5316\u5c0f\u9f20\u6a21\u578b\uff0c\u4ee5\u6a21\u62df\u5c0f\u9f20\u7684\u4eba\u7c7b\u514d\u75ab\u7cfb\u7edf\u3002\u514d\u75ab\u4f4e\u4e0b\u7684NSG\u5c0f\u9f20\u5728\u5168\u8eab\u03b3\u5c04\u7ebf\u7167\u5c04\u540e\uff0c\u7ecf\u5c3e\u9759\u8109\u6ce8\u5c04\u4ebaCD34\uff0b<\/sup>\u9020\u8840\u5e72\u7ec6\u80de\uff0c16\u5468\u540e\u53ea\u91c7\u7528\u4ebaCD45\uff0b<\/sup>\u7ec6\u80de>25%\u7684\u5c0f\u9f20\uff08\u56fe2A\uff09\u3002\u5c06\u643a\u5e26\/\u4e0d\u643a\u5e26ALKBH5\u57fa\u56e0\u6572\u9664\u7684HCT116\u7ec6\u80de\u690d\u5165\u4eba\u6e90\u5316CD34\uff0b<\/sup>\u5c0f\u9f20\u4f53\u5185\u3002\u7ed3\u679c\u53d1\u73b0\uff0cALKBH5\u57fa\u56e0\u6572\u9664\u663e\u8457\u6291\u5236\u4e86\u4eba\u6e90\u5316CD34\uff0b<\/sup>\u5c0f\u9f20\u7684\u80bf\u7624\u751f\u957f\uff08\u56fe2B\uff09\u3002<\/p>\n

\u4e4b\u540e\u4f5c\u8005\u5206\u6790\u4e86\u540c\u79cd\u5f02\u4f53CRC\u79fb\u690d\u5728\u4eba\u6e90\u5316CD34\uff0b<\/sup>\u5c0f\u9f20\u4f53\u5185\u7684\u514d\u75ab\u7ec6\u80de\u6e17\u900f\u60c5\u51b5\u3002MDSCs\u3001NK\u7ec6\u80de\u3001CD4\uff0b<\/sup>T\u7ec6\u80de\u548cCD8\uff0b<\/sup>T\u7ec6\u80de\u7684\u95e8\u63a7\u5982\u56fe2C\u6240\u793a\uff0c\u7ed3\u679c\u8868\u660eALKBH5\u57fa\u56e0\u6572\u9664\u7684\u80bf\u7624\u663e\u793aMDSCs\u51cf\u5c11\uff0c\u4f46NK\u7ec6\u80de\u3001CD4\uff0b<\/sup>T\u7ec6\u80de\u548cCD8\uff0b<\/sup>T\u7ec6\u80de\u7684\u6e17\u900f\u589e\u52a0\uff08\u56fe2D\uff09\uff0c\u8bc1\u5b9eALKBH5\u8bf1\u5bfc\u4e86\u4eba\u7c7b\u7ed3\u76f4\u80a0\u764c\u7684\u514d\u75ab\u6291\u5236\u3002\u901a\u8fc7\u514d\u75ab\u7ec4\u5316\u67d3\u8272\u4e5f\u53d1\u73b0ALKBH5\u7684\u9ad8\u8868\u8fbe\u4e0e\u4eba\u539f\u53d1\u7ed3\u76f4\u80a0\u764c\u7ec4\u7ec7\u4e2dCD8\uff0b<\/sup>T\u7ec6\u80de\u7684\u4f4e\u6e17\u900f\u76f8\u5173\uff08\u56fe2E\uff09\u3002\u4ee5\u4e0a\u7ed3\u679c\u8868\u660eALKBH5\u6709\u52a9\u4e8e\u4eba\u7c7b\u7ed3\u76f4\u80a0\u764c\u7684\u514d\u75ab\u6291\u5236\u5fae\u73af\u5883\u3002<\/p>\n

\u56fe2.\u4eba\u7c7b\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\u4e2d\u7684ALKBH5\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab<\/p>\n

AXIN2\u4fe1\u4f7fRNA\u4e3aALKBH5\u4ecb\u5bfc\u7684m6<\/sup>A\u53bb\u7532\u57fa\u5316\u7684\u9776\u70b9<\/p>\n

\u63a5\u4e0b\u6765\u4f5c\u8005\u8fdb\u4e00\u6b65\u5bf9ALKBH5\u5982\u4f55\u4fc3\u8fdb\u7ed3\u76f4\u80a0\u764c\u751f\u957f\u548c\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab\u8fdb\u884c\u7814\u7a76\uff0c\u4ee5\u63a2\u7d22\u5176\u4f5c\u7528\u7684\u5206\u5b50\u57fa\u7840\u3002\u7531\u4e8eALKBH5\u4f7fm6<\/sup>A\u4fee\u9970\u7684mRNA\u53bb\u7532\u57fa\u5316\uff0c\u7814\u7a76\u4eba\u5458\u901a\u8fc7\u8c03\u63a7ALKBH5\u8868\u8fbe\u540e\u68c0\u6d4bCRC\u7ec6\u80de\u4e2d\u6574\u4f53m6<\/sup>A\u7684\u6c34\u5e73\u3002\u7ed3\u679c\u663e\u793aALKBH5\u7f3a\u5931\u7684HCT116\u548cSW1116\u7ec6\u80de\u4e2d\u6574\u4f53m6<\/sup>A\u6c34\u5e73\u589e\u52a0\uff0c\u800cALKBH5\u7684\u8fc7\u8868\u8fbe\u964d\u4f4e\u4e86\u603bm6<\/sup>A\u6c34\u5e73\u3002\u4e3a\u4e86\u63ed\u793aALKBH5\u7684\u4e0b\u6e38\u9776\u70b9\uff0c\u7814\u7a76\u4eba\u5458\u5728ALKBH5\u88ab\u6572\u9664\/\u672a\u6572\u9664\u7684HCT116\u7ec6\u80de\u4e2d\u8fdb\u884c\u4e86MERIP-seq\u548cRNA-seq\uff08\u56fe3A\uff09\u3002\u5728ALKBH5\u57fa\u56e0\u6572\u9664\u540e\uff0c\u901a\u8fc7RNA-seq\u65b9\u6cd5\u9274\u5b9a\u4e8673\u4e2a\u4e0a\u8c03\u57fa\u56e0\u548c51\u4e2a\u4e0b\u8c03\u57fa\u56e0\uff0c\u8fc7\u5ea6\u8868\u8fbe\u5206\u6790\u8868\u660e\uff0c\u5dee\u5f02\u8868\u8fbe\u57fa\u56e0\u4e3b\u8981\u96c6\u4e2d\u5728Wnt\/\u03b2-Catenin\u4fe1\u53f7\u8f6c\u5bfc\u4e2d\uff08\u56fe3B\uff09\u3002\u63a5\u4e0b\u6765\uff0c\u4f5c\u8005\u5206\u6790\u4e86\u57fa\u4e8eMERIP-seq\u7684m6<\/sup>A\u914d\u7f6e\u6587\u4ef6\u3002\u4e0e\u5bf9\u7167\u76f8\u6bd4\uff0cALKBH5\u57fa\u56e0\u6572\u9664\u589e\u52a0\u4e86\u53ef\u68c0\u6d4b\u5230\u7684m6<\/sup>A\u5cf0\u7684\u6570\u91cf\uff08\u56fe3C\uff09\u3002\u7814\u7a76\u4eba\u5458\u5728HCT116-shNC\u4e2d\u68c0\u6d4b\u523011,942\u4e2am6<\/sup>A\u5cf0\uff0c\u5728HCT116-shALKBH5\u4e2d\u68c0\u6d4b\u523013,514\u4e2am6<\/sup>A\u5cf0\uff08\u56fe3C\uff09\u3002ALKBH5\u7f3a\u5931\u5bfc\u81f4356\u4e2a\u57fa\u56e0\u4e2dm6<\/sup>A\u6c34\u5e73\u663e\u8457\u589e\u52a0\uff08\u56fe3D\uff09\u3002\u4e3a\u4e86\u786e\u5b9aALKBH5-m6<\/sup>A\u8f74\u7684\u4e0b\u6e38\u9776\u70b9\uff0c\u4f5c\u8005\u91cd\u53e0\u4e86\u4eceMERIP-seq\u548cRNA-seq\u4e2d\u786e\u5b9a\u7684\u5019\u9009\u57fa\u56e0\uff08\u56fe3E\uff09\uff0c\u5e76\u53d1\u73b0\u4e865\u4e2a\u6f5c\u5728\u7684ALKBH5\u4e0b\u6e38\u9776\u70b9\uff08AXIN2\u3001RGMB\u3001NGFR\u3001C1orf116\u548cARL4C\uff09\uff08\u56fe3F\uff09\u3002\u5176\u4e2d\uff0c\u5728HCT116\u548cSW1116\u7ec6\u80de\u4e2d\uff0cAXIN2\u5728ALKBH5\u88ab\u6572\u9664\u540e\u6301\u7eed\u88ab\u8bf1\u5bfc\u8868\u8fbe\uff08\u56fe3G\uff09\u3002\u56e0\u6b64\uff0cAXIN2\u53ef\u80fd\u662fALKBH5\u5728\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\u4e2d\u7684\u76f4\u63a5\u9776\u70b9\u3002\u6b64\u5916\uff0cm6<\/sup>A\u514d\u75ab\u6c89\u6dc0\u548cRT-PCR\u8868\u660e\uff0cALKBH5\u7684\u7f3a\u5931\u589e\u52a0\u4e86\u4eba\u7ed3\u80a0\u764c\u7ec6\u80de\u7cfb\uff08HCT116\u548cSW1116\uff09\u548c\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\u7cfb\uff08MC38\u548cCT26\uff09\u4e2dAXIN2 mRNA\u7684m6<\/sup>A\u6c34\u5e73\uff1b\u76f8\u53cd\uff0cALKBH5\u8fc7\u8868\u8fbe\u964d\u4f4e\u4e86HCT116\u548cMC38\u7ec6\u80deAXIN2 mRNA\u4e0a\u7684m6<\/sup>A\u6c34\u5e73\uff08\u56fe3H\uff09\u3002\u63a5\u4e0b\u6765\u4f5c\u8005\u731c\u60f3ALKBH5\u662f\u5426\u80fd\u76f4\u63a5\u4e0eAXIN2 mRNA\u7ed3\u5408\u3002\u4e3a\u6b64\uff0c\u5728HCT116\u548cMC38\u7ec6\u80de\u4e2d\u8fdb\u884c\u4e86\u6297ALKBH5\u6297\u4f53\u7684RNA\u514d\u75ab\u6c89\u6dc0\uff0c\u63ed\u793a\u4e86ALKBH5\u548cAXIN2 mRNA\u4e4b\u95f4\u7684\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\uff08\u56fe3I\uff09\u3002\u7efc\u4e0a\u8868\u660eALKBH5\u4e0eAXIN2 mRNA\u7ed3\u5408\uff0c\u4f7fm6<\/sup>A\u6807\u8bb0\u53bb\u7532\u57fa\u5316\u3002<\/p>\n

\u56fe3.AXIN2\u786e\u5b9a\u4e3aALKBH5\u7684\u5019\u9009\u9776\u70b9<\/p>\n

ALKBH5\u7834\u574fIGF2BP1\u4ecb\u5bfc\u7684AXIN2 mRNA\u7684\u7a33\u5b9a\u6027<\/p>\n

\u4e4b\u540e\uff0c\u4f5c\u8005\u63a2\u8ba8\u4e86ALKBH5\u662f\u5426\u4ee5\u53ca\u5982\u4f55\u5f71\u54cd\u7ed3\u76f4\u80a0\u764c\u4e2dAXIN2\u7684\u8868\u8fbe\u3002\u7814\u7a76\u4eba\u5458\u53d1\u73b0\uff0c\u5728ALKBH5\u7f3a\u5931\u7684CRC\u7ec6\u80de\u4e2d\uff0cAXIN2\u7684mRNA\u548c\u86cb\u767d\u8868\u8fbe\u5747\u663e\u8457\u589e\u52a0\uff08\u56fe4A\uff09\uff0c\u800c\u5176\u8868\u8fbe\u88abALKBH5\u8fc7\u8868\u8fbe\u6291\u5236\uff08\u56fe4B\uff09\u3002\u9274\u4e8em6<\/sup>A\u4fee\u9970\u5bf9mRNA\u8870\u53d8\u6709\u663e\u8457\u5f71\u54cd\uff0c\u4f5c\u8005\u5047\u8bbeALKBH5\u53ef\u4ee5\u8c03\u8282AXIN2 mRNA\u7684\u7a33\u5b9a\u6027\u3002\u7ed3\u679c\u663e\u793aALKBH5\u7f3a\u5931\u786e\u5b9e\u7a33\u5b9a\u4e86AXIN2 mRNA\uff0c\u800cALKBH5\u8fc7\u8868\u8fbe\u5219\u4ea7\u751f\u76f8\u53cd\u7684\u6548\u679c\uff08\u56fe4C\uff09\u3002\u4e3a\u4e86\u63ed\u793a\u4ecb\u5bfcALKBH5\u8bf1\u5bfc\u7684mRNA\u964d\u89e3\u7684m6<\/sup>A readers\uff0c\u7814\u7a76\u4eba\u5458\u5728HCT116\u7ec6\u80de\u4e2d\u6572\u9664\u4e86m6<\/sup>A readers\uff08YTHDF1\/2\/3\u3001YTHDC1\/2\u548cIGF2BP1\/2\/3\uff09\u7684\u8868\u8fbe\uff0c\u53d1\u73b0\u53ea\u6709IGF2BP1\u6572\u4f4e\u663e\u8457\u6291\u5236\u4e86AXIN2 mRNA\u548c\u86cb\u767d\u7684\u8868\u8fbe\uff1b\u6b64\u5916\uff0c\u6297IGF2BP1\u6297\u4f53\u7684RNA\u514d\u75ab\u6c89\u6dc0\u5b9e\u9a8c\u8bc1\u5b9e\u4e86HCT116\u548cMC38\u7ec6\u80de\u4e2dIGF2BP1\u548cAXIN2 mRNA\u4e4b\u95f4\u7684\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\uff08\u56fe4D\uff09\u3002\u6700\u540e\uff0c\u5728CRC\u961f\u5217I\u4e2dALKBH5\u548cAXIN2\u5728\u86cb\u767d\u6c34\u5e73\u4e0a\u7684\u8868\u8fbe\u4ee5\u53ca\u961f\u5217II\u7684mRNA\u6c34\u5e73\u90fd\u5448\u8d1f\u76f8\u5173\uff08\u56fe4E\uff09\u3002\u7efc\u4e0a\u6240\u8ff0\uff0c\u8fd9\u4e9b\u6570\u636e\u8868\u660eALKBH5\u4f7fAXIN2 mRNA\u7684m6<\/sup>A\u53bb\u7532\u57fa\u5316\uff0c\u4ece\u800c\u964d\u4f4eIGF2BP1\u4ecb\u5bfc\u7684AXIN2 mRNA\u7a33\u5b9a\u6027\u3002<\/p>\n

ALKBH5\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d<\/p>\n

\u8bf1\u5bfcm6<\/sup>A-AXIN2-\u03b2-Catenin\u8f74\u7684\u8868\u8fbe<\/p>\n

AXIN2\u4f5c\u4e3a\u03b2-Catenin\u7834\u574f\u590d\u5408\u4f53\u4e2d\u7684\u652f\u67b6\u86cb\u767d\uff0c\u4fc3\u8fdb\u03b2-Catenin\u7684\u964d\u89e3\u3002\u7531\u4e8e\u5728RNA-seq\u5206\u6790\u4e2d\uff0cWnt\/\u03b2-Catenin\u88ab\u786e\u5b9a\u4e3aALKBH5\u7f3a\u5931\u8c03\u8282\u7684\u6700\u9ad8\u4fe1\u53f7\u901a\u8def\uff08\u56fe3B\uff09\uff0c\u4f5c\u8005\u5047\u8bbeALKBH5\u53ef\u80fd\u901a\u8fc7\u6291\u5236AXIN2\u800c\u6fc0\u6d3b\u7ed3\u76f4\u80a0\u764c\u4e2d\u7684Wnt\u4fe1\u53f7\u3002HCT116\u548cSW1116\u7ec6\u80de\u4e2d\u7684ALKBH5\u57fa\u56e0\u6572\u9664\u51cf\u5c11\u4e86\u6838\u03b2-Catenin\u7684\u8868\u8fbe\uff1bWnt\/\u03b2-Catenin\u4fe1\u53f7\u7684\u4e24\u4e2a\u8f6c\u5f55\u9776\u70b9MYC\u548cCyclin D1\u7684\u8868\u8fbe\u5728ALKBH5\u88ab\u6572\u9664\u540e\u663e\u8457\u964d\u4f4e\uff1b\u53cd\u4e4b\uff0cALKBH5\u8fc7\u8868\u8fbe\u8bf1\u5bfcMYC\u548c\u7ec6\u80de\u5468\u671f\u86cb\u767dD1\u7684\u8868\u8fbe\uff08\u56fe4F\uff09\u3002ALKBH5\u57fa\u56e0\u6572\u9664\u4e5f\u6291\u5236\u4e86MC38\u548cCT26\u7ec6\u80de\u4e2d\u6d3b\u6027\u03b2-Catenin\u3001MYC\u548c\u7ec6\u80de\u5468\u671f\u86cb\u767dD1\u7684\u8868\u8fbe\uff0c\u800c\u5728MC38\u7ec6\u80de\u4e2d\u8fc7\u8868\u8fbeALKBH5\u5219\u8d77\u5230\u76f8\u53cd\u7684\u4f5c\u7528\uff08\u56fe4G\uff09\u3002<\/p>\n

\u4e3a\u4e86\u9a8c\u8bc1AXIN2\u662fALKBH5\u548cWnt\/\u03b2-Catenin\u4fe1\u53f7\u4e4b\u95f4\u7684\u5206\u5b50\u94fe\u63a5\uff0c\u7814\u7a76\u4eba\u5458\u5728ALKBH5\u8fc7\u8868\u8fbe\u7684HCT116\u548cMC38\u7ec6\u80de\u4e2d\u5916\u6e90\u5bfc\u5165\u4e86AXIN2\u3002AXIN2\u7684\u91cd\u65b0\u8868\u8fbe\u6d88\u9664\u4e86ALKBH5\u4fc3\u8fdb\u03b2-Catenin\u8868\u8fbe\u548cCRC\u7ec6\u80de\u751f\u957f\u7684\u4f5c\u7528\uff08\u56fe4H\uff09\u3002\u4e14\u53ea\u6709\u91ce\u751f\u578b\uff08WT\uff09ALKBH5\u800c\u975e\u7a81\u53d8\u7684ALKBH5\uff0c\u53ef\u4ee5\u6291\u5236AXIN2\u7684\u8868\u8fbe\uff0c\u5e76\u5728\u5185\u6e90\u6027ALKBH5\u7f3a\u5931\u7684\u60c5\u51b5\u4e0b\u6062\u590dHCT116\u548cSW1116\u7ec6\u80de\u4e2d\u6d3b\u6027\u7684\u03b2-Catenin\uff0c\u8fd9\u610f\u5473\u7740ALKBH5\u4ee5m6<\/sup>A\u4f9d\u8d56\u7684\u65b9\u5f0f\u8bf1\u5bfcWnt\/\u03b2-Catenin\u4fe1\u53f7\u8f6c\u5bfc\uff1b\u540c\u6837WT ALKBH5\u800c\u975e\u7a81\u53d8\u7684ALKBH5\u633d\u6551\u4e86ALKBH5\u57fa\u56e0\u6572\u9664\u5f15\u8d77\u7684\u589e\u6b96\u7f3a\u9677\uff08\u56fe4I\uff09\u3002\u7efc\u4e0a\u7ed3\u679c\u8bc1\u660eALKBH5\u901a\u8fc7m6<\/sup>A-AXIN2-\u03b2-Catenin\u8f74\u4fc3\u8fdbCRC\u3002<\/p>\n

\u56fe4.ALKBH5\u901a\u8fc7\u76f4\u63a5\u8c03\u8282AXIN2 mRNA\u7684m6<\/sup>A\u6c34\u5e73\uff0c\u4fc3\u8fdb\u7ed3\u76f4\u80a0\u764cWnt\/\u03b2-Catenin\u4fe1\u53f7\u8f6c\u5bfc<\/p>\n

ALKBH5\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u8bf1\u5bfcWnt\u9776\u57fa\u56e0DKK1<\/p>\n

WNT\u4fe1\u53f7\u662f\u80bf\u7624\u514d\u75ab\u53cd\u5e94\u7684\u4e3b\u8981\u8c03\u8282\u56e0\u5b50\u3002RNA-seq\u663e\u793a\uff0cWnt\/\u03b2-Catenin\u4fe1\u53f7\u7684\u4e0b\u6e38\u8f6c\u5f55\u57fa\u56e0Dickkopf\u76f8\u5173\u86cb\u767d1\uff08DKK1\uff09\u662fALKBH5\u57fa\u56e0\u6572\u9664\u7684\u6700\u9ad8\u6291\u5236\u57fa\u56e0\uff08\u56fe5A\uff09\u3002ALKBH5\u7f3a\u5931\u65f6\uff0c\u5728\u4eba\uff08HCT116\u548cSW1116\uff09\u548c\u5c0f\u9f20CRC\u7ec6\u80de\u7cfb\uff08MC38\u548cCT26\uff09\u4e2d\u89c2\u5bdf\u5230DKK1\u5728mRNA\u548c\u86cb\u767d\u6c34\u5e73\u7684\u8868\u8fbe\u51cf\u5c11\uff0c\u800cALKBH5\u7684\u8fc7\u8868\u8fbe\u5219\u8d77\u5230\u76f8\u53cd\u7684\u4f5c\u7528\uff08\u56fe5B\uff09\u3002\u7531\u4e8eAXIN2\u53ef\u4ee5\u6291\u5236Wnt\/\u03b2-Catenin\u4fe1\u53f7\u7684\u6fc0\u6d3b\uff0c\u56e0\u6b64\u4f5c\u8005\u7814\u7a76\u4e86AXIN2\u662f\u5426\u53ef\u4ee5\u8c03\u8282DKK1\u7684\u8868\u8fbe\u3002\u7814\u7a76\u53d1\u73b0AXIN2\u7684\u91cd\u65b0\u8868\u8fbe\u6291\u5236\u4e86ALKBH5\u5bf9DKK1\u7684\u8bf1\u5bfc\uff0c\u8fd9\u610f\u5473\u7740ALKBH5\u901a\u8fc7AXIN2\u4fc3\u8fdb\u4e86DKK1\u7684\u8868\u8fbe\uff08\u56fe5C\uff09\u3002\u4e0e\u6b64\u4e00\u81f4\uff0c\u5728\u961f\u5217I\u548c\u961f\u5217II\u7684\u5927\u80a0\u764c\u4e2d\uff0cALKBH5\u548cDKK1\u7684\u8868\u8fbe\u5448\u663e\u8457\u6b63\u76f8\u5173\uff08\u56fe5D\uff09\u3002DKK1\u662f\u4e00\u79cd\u5206\u6ccc\u6027\u86cb\u767d\uff0c\u7814\u7a76\u4eba\u5458\u8fdb\u4e00\u6b65\u68c0\u6d4b\u4e86CRC\u6761\u4ef6\u57f9\u517b\u6db2\u4e2dDKK1\u7684\u6c34\u5e73\u3002\u53d1\u73b0\u53bb\u9664ALKBH5\u663e\u8457\u964d\u4f4e\u4e86\u4eba\uff08HCT116\u548cSW1116\uff09\u548c\u5c0f\u9f20CRC\u7ec6\u80de\u7cfb\uff08MC38\u548cCT26\uff09\u6761\u4ef6\u57f9\u517b\u6db2\u4e2dDKK1\u7684\u6c34\u5e73\uff08\u56fe5E\uff09\uff0c\u4ee5\u53ca\u643a\u5e26MC38\u80bf\u7624\u7684\u5c0f\u9f20\u8840\u6e05\u4e2d\u7684DKK1\u6c34\u5e73\uff08\u56fe5F\uff09\u3002\u76f8\u53cd\uff0c\u8fc7\u8868\u8fbeALKBH5\u5219\u4ea7\u751f\u76f8\u53cd\u7684\u6548\u679c\uff08\u56fe5E\u548cF\uff09\u3002\u7efc\u4e0a\uff0cALKBH5\u901a\u8fc7m6<\/sup>A-AXIN2-\u03b2-Catenin\u8f74\u5171\u540c\u4fc3\u8fdbDKK1\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u7684\u8868\u8fbe\u3002<\/p>\n

\u56fe5.ALKBH5\u901a\u8fc7\u8bf1\u5bfc\u7ed3\u76f4\u80a0\u764c\u7ec6\u80de\u5916\u5206\u6cccDKK1<\/p>\n

\u8bf1\u5bfcMDSCs\u79ef\u805a<\/p>\n

ALKBH5\u901a\u8fc7DKK1\u4fc3\u8fdb\u9aa8\u9ad3\u6e90\u6027\u6291\u5236\u7ec6\u80de\u52df\u96c6<\/p>\n

DKK1\u5df2\u88ab\u62a5\u9053\u4e0eMDSCs\u805a\u96c6\u6709\u5173\u3002\u4f5c\u8005\u63a8\u6d4bALKBH5\u53ef\u80fd\u8bf1\u5bfcDKK1\u5206\u6ccc\u5728\u7ed3\u76f4\u80a0\u764c\u4e2d\u62db\u52dfMDSCs\u3002\u4e3a\u6b64\uff0c\u4ece\u540c\u57fa\u56e0\u5c0f\u9f20\u7ed3\u76f4\u80a0\u764c\u6a21\u578b\u4e2d\u5206\u79bb\u51fa\u813eMDSCs\uff0c\u5c06\u7eaf\u5316MDSCs\u4e0eALKBH5\u7f3a\u5931\/\u672a\u7f3a\u5931\u7684\u5c0f\u9f20CRC\u7ec6\u80de\u5171\u57f9\u517b\uff08\u56fe5G\uff09\u3002\u53d1\u73b0\u4e0e\u5bf9\u7167\u7ec4\u76f8\u6bd4\uff0c\u6765\u81eaALKBH5\u57fa\u56e0\u6572\u9664\u7684MC38\u6216CT26\u7684\u6761\u4ef6\u57f9\u517b\u6db2\u5438\u5f15MDSCs\u8fc1\u79fb\u7684\u80fd\u529b\u964d\u4f4e\uff0c\u800c\u8fd9\u79cd\u5dee\u5f02\u53ef\u901a\u8fc7\u8865\u5145\u91cd\u7ec4DKK1\u86cb\u767d\uff08RDKK1\uff09\u6765\u6d88\u9664\uff0c\u4e14\u91cd\u7ec4DKK1\u4ee5\u5242\u91cf\u4f9d\u8d56\u7684\u65b9\u5f0f\u4fc3\u8fdbMDSC\u8fc1\u79fb\uff08\u56fe5H\uff09\u3002\u56e0\u6b64\uff0cALKBH5\u53ef\u8bf1\u5bfcDKK1\u8868\u8fbe\u4ee5\u52df\u96c6MDSCs\u3002<\/p>\n

\u63a5\u4e0b\u6765\u4f5c\u8005\u731c\u6d4bALKBH5\u662f\u5426\u5f71\u54cdMDSCs\u7684\u529f\u80fd\u3002\u4e3a\u6b64\uff0c\u7814\u7a76\u4eba\u5458\u68c0\u6d4b\u4e86\u6dfb\u52a0\/\u4e0d\u6dfb\u52a0rDKK1\u57f9\u517b\u7684\u79bb\u4f53\u813eMDSCs\u548c\u4ece\u6dfb\u52a0\/\u4e0d\u6dfb\u52a0ALKBH5\u7684MC38\u540c\u79cd\u5f02\u4f53\u79fb\u690d\u7269\u4e2d\u5206\u79bb\u7684\u80bf\u7624\u6d78\u6da6\u6027MDSCs\u7684\u529f\u80fd\u6807\u5fd7\uff08\u56fe5G\uff09\u3002\u7ed3\u679c\u53d1\u73b0\uff0c\u5728\u80bf\u7624\u6d78\u6da6\u6027MDSCs\u4e2d\uff0cALKBH5\u57fa\u56e0\u6572\u9664\u540e\uff0cMDSCs\u7684\u4e24\u4e2a\u529f\u80fd\u6807\u5fd7\u7269\u8bf1\u5bfc\u578b\u4e00\u6c27\u5316\u6c2e\u5408\u9176\uff08iNOS\uff09\u548cArg1\u7684\u8868\u8fbe\u663e\u8457\u964d\u4f4e\u3002\u6b64\u5916\uff0c\u5728\u57f9\u517b\u4e0a\u6e05\u6db2\u4e2d\u6dfb\u52a0rDKK1\u53ef\u589e\u52a0MDSCs\u4e2diNOS\u548cArg1\u7684\u8868\u8fbe\uff08\u56fe5I\uff09\u3002\u4e3a\u4e86\u9a8c\u8bc1DKK1\u5728\u4ecb\u5bfcALKBH5\u8bf1\u5bfc\u7684\u514d\u75ab\u6291\u5236\u4e2d\u7684\u529f\u80fd\u91cd\u8981\u6027\uff0c\u5728\u4f53\u5185\u7528\u6297DKK1\u6297\u4f53\u4e2d\u548cDKK1\u3002\u80bf\u7624\u957f\u523050~100 mm3<\/sup>\u540e\uff0c\u9694\u5929\u8179\u8154\u6ce8\u5c04DKK1\u4e2d\u548c\u6297\u4f53\uff0c\u53d1\u73b0\u6297DKK1\u6cbb\u7597\u53d6\u6d88\u4e86ALKBH5\u5bf9\u80bf\u7624\u751f\u957f\u548cMDSC\u6d78\u6da6\u7684\u4fc3\u8fdb\u4f5c\u7528\uff0c\u4f34\u968f\u7740\u80bf\u7624\u4e2dNK\u7ec6\u80de\u548cCD8+<\/sup> T\u7ec6\u80de\u7684\u6062\u590d\uff08\u56fe5J-K\uff09\u3002\u56e0\u6b64\uff0cALKBH5\u8bf1\u5bfcDKK1\u8868\u8fbe\uff0c\u5c06\u514d\u75ab\u6291\u5236\u7684MDSCs\u52df\u96c6\u5230\u7ed3\u76f4\u80a0\u764c\u80bf\u7624\u5fae\u73af\u5883\u4e2d\u3002<\/p>\n

\u80a0\u9053\u7279\u5f02\u6027Alkbh5\u6572\u5165\u86cb\u767d\u4fc3\u8fdb\u5c0f\u9f20\u7ed3\u76f4\u80a0\u80bf\u7624\u53d1\u751f\u5e76\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab<\/p>\n

\u4e3a\u4e86\u8bc1\u5b9eALKBH5\u5728\u81ea\u53d1\u6027\u7ed3\u76f4\u80a0\u80bf\u7624\u53d1\u751f\u4e2d\u7684\u4f5c\u7528\uff0c\u7814\u7a76\u4eba\u5458\u57f9\u80b2\u4e86\u80a0\u9053\u7279\u5f02\u6027ALKBH5\u6572\u5165\u86cb\u767d\uff08Alkbh5 KI\uff09\u5c0f\u9f20\uff0cAlkbh5 KI\u5c0f\u9f20\u53ca\u5176WT\u5e7c\u9f20\u88ab\u7ed9\u4e88\u5076\u6c2e\u6c27\u7532\u70f7\u52a0DSS\u4ee5\u89e6\u53d1\u80bf\u7624\u5f62\u6210\uff08\u56fe6A\uff09\u3002\u6700\u7ec8\uff0c\u4e0eWT\u540c\u7a9d\u5c0f\u9f20\u76f8\u6bd4\uff0cAlkbh5 KI\u5c0f\u9f20\u7684\u80bf\u7624\u8d1f\u8377\u66f4\u9ad8\u4e14\u80bf\u7624\u66f4\u5927\uff08\u56fe6B\uff09\u3002Ki-67\u67d3\u8272\u7ed3\u679c\u663e\u793a\uff0c\u4e0eWT\u76f8\u6bd4\uff0cAlkbh5 KI\u5c0f\u9f20\u80bf\u7624\u548c\u80a0\u9690\u7a9d\u4e2d\u589e\u6b96\u7ec6\u80de\u6bd4\u4f8b\u589e\u52a0 \uff08\u56fe6C\uff09\u3002TIME\u65b9\u9762\uff0c\u4e0eWT\u5c0f\u9f20\u76f8\u6bd4\uff0cAlkbh5 KI\u5c0f\u9f20\u80bf\u7624\u4e2dMDSC\u6d78\u6da6\u589e\u52a0\uff0c\u4f34\u968f\u7740NK\u548cCD8+<\/sup>T\u7ec6\u80de\u7684\u663e\u8457\u51cf\u5c11\uff08\u56fe6D\uff09\u3002\u514d\u75ab\u8367\u5149\u67d3\u8272\u8bc1\u5b9e\u5728Alkbh5 KI\u5c0f\u9f20\u6765\u6e90\u7684\u80bf\u7624\u4e2d\u6709\u660e\u663e\u7684MDSCs\u79ef\u805a\uff08\u56fe6E\uff09\u3002\u6b64\u5916\uff0c\u4e0eWT\u5c0f\u9f20\u76f8\u6bd4\uff0cAlkbh5 KI\u5c0f\u9f20\u7684\u80bf\u7624\u663e\u793aAXIN2\u8868\u8fbe\u51cf\u5c11\uff0c\u4f46\u6d3b\u6027\u03b2-Catenin\u548cDKK1\u86cb\u767d\u8868\u8fbe\u589e\u52a0\uff08\u56fe6F\uff09\u3002\u8fd9\u4e9b\u7ed3\u679c\u8868\u660e\uff0cAlkbh5\u901a\u8fc7m6<\/sup>A-AXIN2-WNT-DKK1\u8f74\u4fc3\u8fdb\u514d\u75ab\u6291\u5236\u7684\u80bf\u7624\u5fae\u73af\u5883\u8fdb\u800c\u4fc3\u8fdb\u7ed3\u76f4\u80a0\u764c\u7684\u53d1\u751f\u3002<\/p>\n

\u56fe6.Alkbh5\u4fc3\u8fdb\u80a0\u9053\u7279\u5f02\u6027Alkbh5\u6572\u5165\uff08KI\uff09\u5c0f\u9f20\u7684\u7ed3\u80a0\u764c\u53d1\u751f\u5e76\u6291\u5236\u6297\u80bf\u7624\u514d\u75ab<\/p>\n

\u9776\u5411ALKBH5\u6216DKK1\u589e\u5f3a<\/p>\n

\u6297PD1\u6cbb\u7597\u5bf9\u7ed3\u76f4\u80a0\u764c\u7684\u6291\u5236\u4f5c\u7528<\/p>\n

\u9274\u4e8eALKBH5\u8bf1\u5bfcDKK1\u5206\u6ccc\u62db\u52df\u6291\u5236\u6027MDSCs\u4ee5\u51cf\u5f31\u6297\u7ed3\u76f4\u80a0\u764c\u514d\u75ab\u53cd\u5e94\uff0c\u4f5c\u8005\u7814\u7a76\u4e86\u9776\u5411ALKBH5\u6216DKK1\u662f\u5426\u53ef\u4ee5\u63d0\u9ad8\u6297PD1\u6cbb\u7597\u7684\u7597\u6548\u3002\u4e3a\u4e86\u5728\u4f53\u5185\u9776\u5411ALKBH5\uff0c\u7814\u7a76\u4eba\u5458\u4f7f\u7528\u56e2\u961f\u7814\u53d1\u7684VNP\u7cfb\u7edf\u5c06\u7279\u5b9a\u7684ALKBH5-siRNA\u8f93\u9001\u5230\u80bf\u7624\u4e2d\uff0c\u4e4b\u540e\u7528VNP-siNC\u6216VNP-siALKBH5\u6cbb\u7597MC38\u540c\u57fa\u56e0\u80bf\u7624\u6a21\u578b\uff0c\u7ed9\u4e88\/\u4e0d\u7ed9\u4e88\u6297PD1\u6cbb\u7597\uff0c\u7ed3\u679c\u53d1\u73b0\u4e0eVNP-siNC\u76f8\u6bd4\uff0cVNP-siALKBH5\u663e\u8457\u6291\u5236\u4e86MC38\u540c\u79cd\u5f02\u4f53\u79fb\u690d\u7269\u7684\u751f\u957f\uff0c\u4e14VNP-siALKBH5\u8054\u5408\u6297PD1\u6cbb\u7597\u5bf9MC38\u540c\u79cd\u5f02\u4f53\u79fb\u690d\u7269\u7684\u751f\u957f\u6291\u5236\u4f5c\u7528\u6700\u5f3a\uff08\u56fe7A\u548cB\uff09\u3002VNP-siALKBH5\u8054\u5408\u6297PD1\u6cbb\u7597\u663e\u8457\u51cf\u5c11\u4e86MDSCs\u5728\u80bf\u7624\u5185\u7684\u805a\u96c6\uff0c\u800cCD8+<\/sup>T\u7ec6\u80de\u548cNK\u7ec6\u80de\u7684\u6d78\u6da6\u589e\u52a0\uff08\u56fe7C\uff09\u3002\u6b64\u5916\uff0c\u8054\u5408\u6cbb\u7597\u7ec4\u7684MC38\u540c\u79cd\u5f02\u4f53\u79fb\u690d\u7269\u4e2d\u9897\u7c92\u9176B+<\/sup>\u3001\u80bf\u7624\u574f\u6b7b\u56e0\u5b50\u03b1+<\/sup>\u548c\u5e72\u6270\u7d20\u03b3+<\/sup> CD8+<\/sup>T\u7ec6\u80de\u7684\u8868\u8fbe\u6c34\u5e73\u6700\u9ad8\uff08\u56fe7D\uff09\u3002\u56e0\u6b64\uff0c\u9776\u5411ALKBH5\u53ef\u589e\u5f3a\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u6cbb\u7597\u7ed3\u76f4\u80a0\u764c\u7684\u7597\u6548\u3002<\/p>\n

\u63a5\u4e0b\u6765\uff0c\u4f5c\u8005\u63a2\u8ba8\u4e86\u963b\u65adDKK1\u662f\u5426\u4e5f\u589e\u5f3a\u4e86\u6297PD1\u6cbb\u7597\u7684\u7597\u6548\u3002\u91c7\u7528\u6297DKK1\u3001\u6297PD1\u6216\u7ec4\u5408\u6cbb\u7597MC38\u80bf\u7624\uff0c\u4e0e\u5bf9\u7167\u7ec4\u76f8\u6bd4\uff0c\u6297DKK1\u6216\u6297PD1\u6cbb\u7597\u5747\u663e\u8457\u6291\u5236\u80bf\u7624\u4f53\u79ef\u548c\u91cd\u91cf\uff0c\u800c\u7ec4\u5408\u6cbb\u7597\u5bf9\u80bf\u7624\u7684\u6291\u5236\u4f5c\u7528\u6700\u5f3a\uff08\u56fe7E\u548cF\uff09\u3002\u4e0e\u5bf9\u7167\u7ec4\u76f8\u6bd4\uff0c\u8054\u5408\u5e94\u7528\u6297DKK1\u548c\u6297PD1\u53ef\u663e\u8457\u51cf\u5c11MC38\u540c\u79cd\u5f02\u4f53\u79fb\u690d\u7269\u4e2d\u7684MDSCs\uff0c\u589e\u52a0CD8+<\/sup>T\u7ec6\u80de\u548cNK\u7ec6\u80de\u7684\u6d78\u6da6\uff08\u56fe7G\uff09\uff0c\u4e14\u7ec4\u5408\u6cbb\u7597\u8bf1\u5bfc\u4e86\u6700\u5f3a\u7684\u6297\u80bf\u7624\u514d\u75ab\u53cd\u5e94\uff08\u56fe7H\uff09\u3002\u56e0\u6b64\uff0c\u6297DKK1\u6297\u4f53\u53ef\u589e\u5f3a\u7ed3\u76f4\u80a0\u764c\u5bf9\u6297PD1\u6297\u4f53\u7684\u6cbb\u7597\u53cd\u5e94\u3002<\/p>\n

\u56fe7.VNP-siALKBH5\/\u6297DKK1\u52a0\u6297PD-1\u8054\u5408\u6cbb\u7597\u53ef\u534f\u540c\u6291\u5236\u8fc7\u8868\u8fbeALKBH5\u7684MC38\u5f02\u4f53\u79fb\u690d\u7269\u7684\u751f\u957f<\/p>\n

\u603b<\/p>\n

\u7ed3<\/p>\n

\u603b\u7684\u6765\u8bf4\uff0c\u672c\u7814\u7a76\u53d1\u73b0\u7ed3\u76f4\u80a0\u764c\u4e2dALKBH5\u7684\u8868\u8fbe\u901a\u8fc7m6<\/sup>A-AXIN2-WNT-DKK1\u8f74\u62db\u52df\u9aa8\u9ad3\u6e90\u6027\u6291\u5236\u7ec6\u80de\uff0c\u6291\u5236\u6297\u80bf\u7624CD8+<\/sup> T\u548c\u81ea\u7136\u6740\u4f24\u7ec6\u80de\u7684\u6e17\u900f\u3002\u63d0\u793a\u9776\u5411ALKBH5\u6216DKK1\u53ef\u91cd\u65b0\u6fc0\u6d3b\u6297\u80bf\u7624\u514d\u75ab\uff0c\u5e76\u4e0e\u6297PD1\u514d\u75ab\u68c0\u67e5\u70b9\u963b\u65ad\u6cbb\u7597\u534f\u540c\u6291\u5236\u7ed3\u76f4\u80a0\u764c\u751f\u957f\u3002\u6b64\u5916\u53d1\u73b0\u5728\u591a\u4e2a\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u961f\u5217\u4e2d\uff0cALKBH5\u7684\u9ad8\u8868\u8fbe\u4e0e\u9884\u540e\u4e0d\u826f\u76f8\u5173\uff0cALKBH5\u53ef\u80fd\u662f\u5224\u65ad\u7ed3\u76f4\u80a0\u764c\u60a3\u8005\u9884\u540e\u7684\u6f5c\u5728\u6307\u6807\u3002<\/p>\n

\u5168\u6587\u603b\u7ed3\u56fe<\/p>\n

Zhai J, Chen H, Wong CC, Peng Y, Gou H, Zhang J, Pan Y, Chen D, Lin Y, Wang S, Kang W, To KF, Chen Z, Nie Y, He HH, Sung JJ, Yu J. ALKBH5 Drives Immune Suppression Via Targeting AXIN2 to Promote Colorectal Cancer and Is a Target for Boosting Immunotherapy. Gastroenterology. 2023 Aug;165(2):445-462.<\/p>\n

\u672c\u6587\u4f5c\u8005<\/p>\n

\u6768\u4e9a\u83b2<\/p>\n

\u4e2d\u56fd\u836f\u79d1\u5927\u5b66 \u836f\u7406\u5b66\u7855\u58eb<\/p>\n","protected":false},"excerpt":{"rendered":"

\u7ed3\u76f4\u80a0\u764c\uff08CRC\uff09\u4e3a\u5e38\u89c1\u764c\u75c7\u4e4b\u4e00\uff0c\u7531\u4e8e\u80bf\u7624\u7684\u8f6c\u79fb\u548c\u590d\u53d1\uff0cCRC\u6b7b\u4ea1\u7387\u5c45\u9ad8\u4e0d\u4e0b\u3002\u7ed3 … \u7ee7\u7eed\u9605\u8bfb →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[70],"tags":[],"class_list":["post-46324","post","type-post","status-publish","format-standard","hentry","category-70"],"_links":{"self":[{"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=\/wp\/v2\/posts\/46324","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=46324"}],"version-history":[{"count":0,"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=\/wp\/v2\/posts\/46324\/revisions"}],"wp:attachment":[{"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=46324"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=46324"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/zydq.1006ss.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=46324"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}