Long noncoding RNAs play significant roles in diverse cancers. In this study, we found that LINC00240 expression was markedly increased in cervical cancer. Functional in vitro assays in cervical cancer cells showed that LINC00240 enhanced the growth, migration, and invasion of cervical cancer cells. The target of LINC00240 was confirmed as microRNA(miR)-124-3p. Inhibition of miR-124-3p significantly enhanced cervical cancer progression via targeting of STAT3, which is greatly activated in tumor-infiltrating immune cells. LINC00240 expression was able to induce STAT3 expression via sponging of miR-124-3p, and showed a positive association with STAT3 expression in cervical cancer tissues. MHC class I-related chain (MIC)-A plays a key role in activating natural killer T (NKT) cells and serves as a downstream target of STAT3. Here, MICA was inhibited by up-regulation of LINC00240, and could be rescued by STAT3 knockdown. In addition, LINC00240 overexpression suppressed the cytotoxic activity of NKT cells by affecting the STAT3/MICA axis. Subsequently, we found that LINC00240 expression promoted cervical cancer progression via induction of miR-124-3p/STAT3/MICA-mediated NKT cell tolerance. Considering these findings, we conclude that LINC00240 might be a novel target for cervical cancer.

中文翻译：

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LINC00240 / microRNA-124-3p / STAT3 / MICA轴促进了宫颈癌中自然杀伤性T细胞的细胞毒活性。

长的非编码RNA在多种癌症中起重要作用。在这项研究中，我们发现LINC00240表达在宫颈癌中显着增加。宫颈癌细胞的功能性体外测定表明，LINC00240增强了宫颈癌细胞的生长，迁移和侵袭。确认LINC00240的靶标为microRNA（miR）-124-3p。通过靶向STAT3，miR-124-3p的抑制显着增强了宫颈癌的进展，而STAT3则在浸润肿瘤的免疫细胞中被大大激活。LINC00240表达能够通过海绵miR-124-3p诱导STAT3表达，并且在宫颈癌组织中与STAT3表达呈正相关。MHC I类相关链（MIC）-A在激活自然杀伤T（NKT）细胞中起关键作用，并作为STAT3的下游靶标。这里，MICA被LINC00240的上调抑制，并可以通过STAT3敲低来挽救。此外，LINC00240过表达通过影响STAT3 / MICA轴抑制了NKT细胞的细胞毒性活性。随后，我们发现LINC00240表达通过诱导miR-124-3p / STAT3 / MICA介导的NKT细胞耐受性促进宫颈癌的进展。考虑到这些发现，我们得出结论，LINC00240可能是宫颈癌的新靶标。