Chen Li, Ma Ruifeng, Wu Lei, Wang Dandan, Li Jingchao, Guo Li
The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology, No.41 Linyin Road, Kundulun District, Baotou City, 014010, Inner Mongolia, China.
Reprod Sci. 2025 Jun 24. doi: 10.1007/s43032-025-01919-2.
Ovarian cancer (OC) poses a health burden of women. Long non-coding RNA SNHG15 has been reported to promote OC progression; however, its effect on immune evasion remains unknown. Here, we investigated the effect of SNHG15 on OC cell immune evasion and the underlying mechanism. Cell phenotypes were assessed using cell counting kit-8, colony formation, lactate dehydrogenase cytotoxicity, and enzyme-linked immunosorbent assays. The mechanism was evaluated by dual-luciferase reporter assay, RNA pull-down, RNA immunoprecipitation (RIP), methylated RIP, and RNA stability assay. The role in vivo was analyzed using tumor-bearing mice. The results showed that SNHG15 and PD-L1 levels were increased, while miR-545-3p expression was reduced in OC. SNHG15 was a sponge of miR-545-3p, and PD-L1 was a downstream target of SNHG15. Knockdown of SNHG15 suppressed OC cell proliferation, and enhanced cytotoxicity and pro-inflammatory response of CD8 T cells, whereas miR-545-3p downregulation reversed these cellular behaviors. Moreover, PD-L1 reversed the cell phenotypes induced by miR-545-3p. Additionally, SNHG15 was modified by m5C, which was mediated by NSUN2. Furthermore, SNHG15 knockdown impeded tumor growth in mice. In conclusion, m5C-methylated lncRNA SNHG15 promotes OC progression by accelerating cell proliferation and immune evasion via the miR-545-3p/PD-L1 axis, demonstrating a tumor-promoting function of SNHG15 in OC.
卵巢癌（OC）给女性带来健康负担。据报道，长链非编码RNA SNHG15可促进OC进展；然而，其对免疫逃逸的影响尚不清楚。在此，我们研究了SNHG15对OC细胞免疫逃逸的影响及其潜在机制。使用细胞计数试剂盒-8、集落形成、乳酸脱氢酶细胞毒性和酶联免疫吸附测定来评估细胞表型。通过双荧光素酶报告基因测定、RNA下拉、RNA免疫沉淀（RIP）、甲基化RIP和RNA稳定性测定来评估机制。使用荷瘤小鼠分析其在体内的作用。结果显示，OC中SNHG15和PD-L1水平升高，而miR-545-3p表达降低。SNHG15是miR-545-3p的海绵，PD-L1是SNHG15的下游靶点。敲低SNHG15可抑制OC细胞增殖，并增强CD8 T细胞的细胞毒性和促炎反应，而miR-545-3p下调可逆转这些细胞行为。此外，PD-L1可逆转miR-545-3p诱导的细胞表型。另外，SNHG15由NSUN2介导进行m5C修饰。此外，敲低SNHG15可抑制小鼠肿瘤生长。总之，m5C甲基化的lncRNA SNHG15通过miR-545-3p/PD-L1轴加速细胞增殖和免疫逃逸，促进OC进展，证明了SNHG15在OC中的促肿瘤功能。
