Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, 215006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
Department of Operating Room, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
Arch Biochem Biophys. 2018 Nov 15;658:7-15. doi: 10.1016/j.abb.2018.09.019. Epub 2018 Sep 21.
It is commonly recognized that aberrant expression of long non-coding RNAs (lncRNAs) is an important cause of cancer progression. The oncogenic property of KCNQ1OT1 has been identified in several malignant tumors. Here, we decided to explore the biological function and molecular mechanism of KCNQ1OT1 in cholangiocarcinoma (CCA). The expression conditions of KCNQ1OT1 in different tissues and cell lines were examined with qRT-PCR analysis. As expected, KCNQ1OT1 was highly expressed in CCA tissues and cell lines. Results of functional assays revealed the oncogenic function of KCNQ1OT in cholangiocarcinoma progression. The positive effect of KCNQ1OT1 on cell proliferation, invasion and epithelial-mesenchymal transition was identified by performing MTT assay, colony formation assay, transwell invasion assay and western blotting. Whereas, the negative effect of KCNQ1OT1 on the cell apoptosis was tested with flow cytometry analysis. Mechanism investigation revealed that KCNQ1OT1 can act as a ceRNA to improve CCA progression by regulating miR-140-5p/SOX4 axis. Recue assays were conducted to demonstrate the actual effects of KCNQ1OT1-miR-140-5p-SOX4 pathway on CCA progression.
人们普遍认为，长链非编码 RNA（lncRNA）的异常表达是癌症进展的一个重要原因。KCNQ1OT1 的致癌特性已在几种恶性肿瘤中得到证实。在这里，我们决定探讨 KCNQ1OT1 在胆管癌（CCA）中的生物学功能和分子机制。通过 qRT-PCR 分析检测了 KCNQ1OT1 在不同组织和细胞系中的表达情况。正如预期的那样，KCNQ1OT1 在 CCA 组织和细胞系中高表达。功能分析结果揭示了 KCNQ1OT1 在胆管癌进展中的致癌功能。通过 MTT 分析、集落形成分析、Transwell 侵袭分析和 Western blot 检测，确定了 KCNQ1OT1 对细胞增殖、侵袭和上皮-间充质转化的正向作用。然而，通过流式细胞术分析检测了 KCNQ1OT1 对细胞凋亡的负向作用。机制研究表明，KCNQ1OT1 可以作为 ceRNA 通过调节 miR-140-5p/SOX4 轴来改善 CCA 的进展。进行挽救实验以证明 KCNQ1OT1-miR-140-5p-SOX4 通路对 CCA 进展的实际影响。
