Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, PR China; Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China.
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):223-230. doi: 10.1016/j.bbrc.2018.11.012. Epub 2018 Nov 14.
Long non-coding RNAs (lncRNAs) are a crucial member of the non-coding RNA family, and increasing evidence demonstrates that lncRNAs participate in the initiation and progression of cancers. Our study aimed to explore the role of the lncRNA LINC00165 in gastric cancer (GC) development. In the present study, our results showed that LINC00165 was upregulated in GC tissues and cell lines and high expression of LINC00165 was correlated with tumor-node-metastasis stage, invasion depth, and overall survival of GC patients. Functional assays showed that LINC00165 knockdown inhibited the proliferation, migration and invasion of GC cells and LINC00165 overexpression stimulated their proliferation, migration and invasion. Online transcription factor binding site prediction analysis showed that there were STAT3 binding sites in the LINC00165 promoter region. Furthermore, luciferase reporter and chromatin immunoprecipitation assays provided evidence that STAT3 could bind directly to the region between -547 bp to -537 bp (ATGTTGGGAAA) of LINC00165 promoter and activate its transcription. Then GC cells were partitioned into nuclear and cytoplasmic fractions and we found that LINC00165 was localized preferentially to the nucleus. Mechanistically, we revealed that LINC00165 functioned as a scaffold for interaction with Polycomb Repressive Complex 2 to promote the epithelial-mesenchymal transition in GC cells. Taken together, our study revealed that LINC00165 was involved in the progression and poor prognosis of GC as an oncogenic role. Therefore, LINC00165 might become a new potential target for GC chemotherapy and further predict prognosis of patients.
长链非编码 RNA（lncRNA）是非编码 RNA 家族的重要成员，越来越多的证据表明 lncRNA 参与了癌症的发生和发展。我们的研究旨在探索 lncRNA LINC00165 在胃癌（GC）发展中的作用。在本研究中，我们的结果表明 LINC00165 在 GC 组织和细胞系中上调，并且 LINC00165 的高表达与 GC 患者的肿瘤-淋巴结-转移分期、浸润深度和总生存率相关。功能分析表明，LINC00165 敲低抑制了 GC 细胞的增殖、迁移和侵袭，而 LINC00165 的过表达则刺激了它们的增殖、迁移和侵袭。在线转录因子结合位点预测分析表明，在 LINC00165 启动子区域存在 STAT3 结合位点。此外，荧光素酶报告基因和染色质免疫沉淀实验提供了证据，表明 STAT3 可以直接结合到 LINC00165 启动子区域的-547 bp 到-537 bp（ATGTTGGGAAA）之间，并激活其转录。然后将 GC 细胞分离为核和细胞质部分，我们发现 LINC00165 优先定位于细胞核。在机制上，我们揭示了 LINC00165 作为与多梳抑制复合物 2 相互作用的支架，促进 GC 细胞的上皮-间充质转化。总之，我们的研究表明，LINC00165 作为一种致癌作用参与了 GC 的进展和预后不良。因此，LINC00165 可能成为 GC 化疗的新潜在靶点，并进一步预测患者的预后。
