ngµç×ÓÓÎÏ·ÐÂÎÅÍøÑ¶£¨Í¨Ñ¶Ô±ÍõÀòÄÈ£©¿ËÈÕ£¬£¬£¬ngµç×ÓÓÎÏ·Á¥ÊôµÚÒ»Ò½Ôº¾«×¼Ò½Ñ§Ñо¿ÔºÐÅÓÃÔº³¤ÓÚ¾ý½ÌÊÚÍŶÓÑо¿Ð§¹û¡°Targeting N6-methyladenosine reader YTHDF1 with siRNA boosts anti-tumor immunity in NASH-HCC by inhibiting EZH2-IL-6 axis¡±½ÒÏþÓÚ¸ÎÔ༲²¡ÁìÓò¶¥¼¶ÆÚ¿¯Journal of Hepatology ÔÓÖ¾£¨IF=26£©¡£¡£¡£¸ÃÑо¿Ê×´ÎÕ¹ÏÖÁËYTHDF1ÔڷǾƾ«ÐÔÖ¬·¾¸ÎÑ×µ¼ÖµĸÎϸ°û°©£¨NASH-HCC£©ÖеĹ¦Ð§×÷Óᢡ¢·Ö×Ó»úÖÆ¼°ÆäÓëÖ×ÁöÃâÒß΢ÇéÐεÄÏ໥×÷Ó㬣¬£¬Îª¸ÄÉÆNASH-HCC¿¹PD-1ÄÍÒ©ÌṩÁËÁªºÏÖÎÁÆÐÂÕ½ÂÔ¡£¡£¡£
¸Îϸ°û°©(HCC)ÊÇÌìÏÂÉϵÚÁù´ó×î³£Õï¶ÏµÄ°©Ö¢£¬£¬£¬Ò²ÊǵÚÈý´ó°©Ö¢éæÃüÔÒò¡£¡£¡£·Ç¾Æ¾«ÐÔÖ¬·¾¸ÎÑ×(NASH)ÊÇÖ¸³ý¾Æ¾«ºÍÆäËûÃ÷È·µÄ¸ÎËðÒòËØÖ®Íâµ¼ÖµĸÎϸ°ûÄÚÖ¬·¾Ì«¹ý³Á»ýΪÖ÷ÒªÌØÕ÷µÄÁÙ´²²¡Àí×ÛºÏÕ÷£¬£¬£¬Óë·ÊÅÖ¡¢¡¢ÒȵºËØ·´¿¹ºÍ¸ß֬Ѫ֢Óйأ¬£¬£¬×îÖÕ¿ÉÄÜ¿ªÕ¹Îª¸ÎÏËά»¯¡¢¡¢¸ÎÓ²»¯ºÍ¸Î°©¡£¡£¡£Ëæ×ÅÉúÑÄˮƽµÄÌá¸ß£¬£¬£¬NASHÏà¹ØµÄ¸Î°©(NASH-HCC)Õ¼¸Î°©»¼ÕߵıÈÀýÒ²Ô½À´Ô½¸ß¡£¡£¡£
È»¶ø£¬£¬£¬NASH-HCCµÄ±¬·¢ÆøÖÆÉв»ÇåÎú£¬£¬£¬È±·¦ÓÐÓõİÐÏòÒ©Îï¶ÔNASH-HCC¾ÙÐÐÖÎÁÆ¡£¡£¡£ÏÖÔÚΪֹ£¬£¬£¬ÁÙ´²ÉÐδÓÐNASH-HCCµÄÒ©Îï»òÕßÉúÎïÁÆ·¨¡£¡£¡£Ê¹Óõ¥¿Ë¡¿¹Ìå°ÐÏòÃâÒß¼ì²éµã×è¶Ï£¨ICB£©ÒѳÉΪHCCµÄÒ»ÖÖÐÂÐËÖÎÁÆÊֶΣ¬£¬£¬È»¶øNASH-HCC¶ÔICBÖÎÁÆÃ»ÓÐÏìÓ¦£¬£¬£¬Òò´ËؽÐè̽ÌÖNASH-HCC¶ÔICBÖÎÁÆÄÍÒ©µÄÔÒò£¬£¬£¬Ñ°ÕÒNASH-HCCDZÔÚµÄÖÎÁưе㣬£¬£¬´Ó¶øÕ½Ê¤NASH-HCC¶ÔICBÖÎÁÆÄÍÒ©¡£¡£¡£
m6AÊÇÕæºËmRNAÖÐ×ºñµÄ»¯Ñ§ÐÞÊΣ¬£¬£¬¼ÓÈëµ÷ÀíRNAµÄÎȹÌÐÔ¡¢¡¢ºË¼Ó¹¤¡¢¡¢×ªÔË¡¢¡¢¶¨Î»¡¢¡¢·Ò룬£¬£¬ËüºÍRNA-ÂѰ×Ï໥×÷ÓÃÀ´µ÷ÀíRNAµÄÔËÆø¡£¡£¡£YTH N6-¼×»ùÏÙÜÕRNAÁ¬ÏµÂѰ×1 (YTHDF1) ÊÇRNA m6AÐÞÊεġ°ÔĶÁÆ÷¡±ÂѰף¬£¬£¬¿ÉÒÔͨ¹ýYTH½á¹¹ÓòÌØÒìÐÔµÄʶ±ðRNAÉÏm6AÐÞÊεÄλµã£¬£¬£¬Ôö½øºËÌÇÌ帽×ÅÔÚº¬ÓÐm6AÐÞÊεÄmRNAÉÏ¡£¡£¡£È»¶ø¹ØÓÚYTHDF1ÔÚHCC£¬£¬£¬ÌØÊâÊÇNASH-HCCµÄ·¢²¡»úÖÆÖеÄ×÷Ó㬣¬£¬ÒÔ¼°¶ÔÖ×ÁöÃâÒß΢ÇéÐεĵ÷Àí¹¦Ð§£¬£¬£¬ÏÖÔÚ»¹ÖªÖ®ÉõÉÙ¡£¡£¡£
¸ÃÑо¿·¢Ã÷YTHDF1ÔÚNASH-HCC»¼ÕßÖ×Áö×éÖ¯ÖÐÏà½ÏÓÚÖ×ÁöÖÜΧ×éÖ¯ÏÔÖøÉý¸ß¡£¡£¡£Ê¹ÓÃYthdf1¸ÎÔàÌØÒìÐÔ¹ý±í´ïСÊóÒÔ¼°Òûʳģ×ÓÓÕµ¼µÄNASH-HCC×Ô¾õ³ÉÁöÄ£×Ó£¬£¬£¬¸ÃÑо¿·¢Ã÷Ythdf1¿ÉÒÔÔö½øNASH-HCCµÄ±¬·¢ºÍ¿ªÕ¹¡£¡£¡£RNA seq Ч¹ûÌáÐÑYthdf1Ö÷ÒªÓ°ÏìÃâÒßϵͳÏà¹ØÐźÅͨ·£¬£¬£¬sc-RNA seq ºÍÁ÷ʽÆÊÎöЧ¹ûÏÔʾYthdf1ÓÕµ¼ËèÔ´ÐÔÒÖÖÆÏ¸°û£¨MDSCs£©µÄ»ýÀÛ²¢ÒÖÖÆÏ¸°û¶¾ÐÔCD8+T ϸ°ûµÄ¹¦Ð§¡£¡£¡£
MDSCsµÄÕÙļºÍ¹¦Ð§Ö÷ÒªÊܵ½Ï¸°ûÒò×ӵĵ÷¿Ø£¬£¬£¬ÎªÁËÑо¿Ythdf1ÔõÑùÓ°ÏìMDSCsµÄ¹¦Ð§£¬£¬£¬¸ÃÑо¿Í¨Ï꾡°ûÒò×ÓELISA array Á¬ÏµÖ×Áöϸ°ûÓëÃâÒßϸ°ûÌåÍâ¹²×÷ÓýʵÑé·¢Ã÷Ythdf1ͨ¹ýÓÕµ¼IL-6µÄÉøÍ¸£¬£¬£¬½éµ¼MDSCsµÄÕÙļºÍ¼¤»î£¬£¬£¬µ¼ÖÂϸ°û¶¾ÐÔCD8+T ϸ°û¹¦Ð§Õϰ¡£¡£¡£Í¨m6A-seq£¬£¬£¬RIP-seq£¬£¬£¬ribo-seqºÍÂѰ×ÖÊ×éµÈ¶à×éѧÑо¿ÅжϳöEZH2 mRNA ÊÇYTHDF1µÄÒªº¦ÏÂÓΰе㡣¡£¡£YTHDF1ʶ±ðEZH2 mRNA ÉÏm6AÐÞÊÎλµãÔö½øEZH2µÄ·Ò룬£¬£¬EZH2½øÒ»²½Ôö½øIL-6µÄ±í´ïºÍÉøÍ¸¡£¡£¡£LNP°ü¹üsiRNAÖÎÁÆÊÇFDAÅú×¼µÄ¿ÉÓÃÓÚÁÙ´²ÖÎÁƵķ½°¸£¬£¬£¬LNP-siRNA»òÕßYthdf1»ùÒòÇóý°ÐÏòYthdf1ÁªºÏanti-PD-1ÖÎÁÆ¿ÉÏÔÖøÌá¸ßNASH-HCCÖ×Áö¶ÔICBÖÎÁƵÄÃô¸ÐÐÔ¡£¡£¡£
¸ÃÑо¿Ê״η¢Ã÷YTHDF1-EZH2-IL-6ÐźÅÖá¿ÉÒÔÕÐļºÍ¼¤»îMDSCs£¬£¬£¬µ¼ÖÂϸ°û¶¾ÐÔCD8+Tϸ°û¹¦Ð§Õϰ£¬£¬£¬´Ó¶øÔö½øNASH-HCCµÄ±¬·¢ºÍ¿ªÕ¹¡£¡£¡£°ÐÏòYTHDF1¿ÉÒÔÌá¸ßNASH-HCC¿¹anti-PD1ÃâÒßÖÎÁÆÓ¦´ðае㡣¡£¡£

YTHDF1-EZH2-IL-6ÐźÅÖáÔö½øNASH-HCCʾÒâͼ
ngµç×ÓÓÎÏ·Á¥ÊôµÚÒ»Ò½Ôº¾«×¼Ò½Ñ§Ñо¿ÔºÐÅÓÃÔº³¤ÓÚ¾ý½ÌÊÚΪ¸ÃÂÛÎÄͨѶ×÷Õߣ¬£¬£¬ÌØÆ¸¸±Ñо¿Ô±ÍõÀòÄÈΪµÚÒ»×÷Õß¡£¡£¡£
ÂÛÎÄÁ´½Ó£º£º£ºhttps://www.journal-of-hepatology.eu/article/S0168-8278(23)04986-3/fulltext