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Abstract：
SNHG3, a long noncoding RNA (lncRNA), has been linked to poor outcomes in patients with liver hepatocellular carcinoma (LIHC). In this study, we found that SNHG3 was overexpressed in LIHC and associated with poor outcomes in patients with LIHC. Functional assays, including colony formation, spheroid formation, and in vivo assays showed that SNHG3 promoted stemness of cancer stem cells (CSC) and tumor growth in vivo by interacting with microRNA-502-3p (miR-502-3p). miR-502-3p inhibitor repressed the tumor-suppressing effects of SNHG3 depletion. Finally, by RNA pull-down, dual-luciferase reporter assay, m6A methylation level detection, and m6A-IP-qPCR assays, we found that miR-502-3p targeted YTHDF3 to regulate the translation of integrin alpha-6 (ITGA6) and targeted HBXIP to inhibit the m6A modification of ITGA6 through methyltransferase-like 3 (METTL3). Our study revealed that SNHG3 controls the YTHDF3/ITGA6 and HBXIP/METTL3/ITGA6 pathways by repressing miR-502-3p expression to sustain the self-renewal properties of CSC in LIHC.
摘要：
SNHG3，一种长非编码RNA（lncRNA），与肝细胞癌（LIHC）患者的不良预后有关。在这项研究中,我们发现SNHG3在LIHC中过度表达,并且与LIHC患者的不良结局相关.功能测定，包括菌落形成,球状体形成,和体内分析显示SNHG3通过与microRNA-502-3p（miR-502-3p）相互作用促进体内肿瘤干细胞（CSC）的干性和肿瘤生长。miR-502-3p抑制剂抑制SNHG3耗竭的肿瘤抑制作用。最后,通过RNA下拉，双荧光素酶报告分析，m6A甲基化水平检测，和m6A-IP-qPCR检测，我们发现miR-502-3p靶向YTHDF3调节整合素α-6(ITGA6)的翻译,靶向HBXIP通过甲基转移酶样3(METTL3)抑制ITGA6的m6A修饰.我们的研究表明，SNHG3通过抑制miR-502-3p表达来控制YTHDF3/ITGA6和HBXIP/METTL3/ITGA6途径，以维持LIHC中CSC的自我更新特性。
