Zhang Xiaotian, Zhang Xinju, Liu Xiaomin, Qi Pengfei, Wang Huimin, Ma Zhongliang, Chai Yimin
Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Laboratory for Noncoding RNA and Cancer, School of Life Sciences, Shanghai University, Shanghai 200444, P.R. China.
Int J Oncol. 2019 Jan;54(1):199-208. doi: 10.3892/ijo.2018.4599. Epub 2018 Oct 19.
Non-small cell lung cancer (NSCLC) is one of the most common types of cancer worldwide and has the highest mortality rate in China. MicroRNAs (miRNAs or miRs) are involved in tumorigenesis and their important role in cancer is becoming increasingly apparent. The expression of miR‑296‑5p in particular has been shown to be significantly downregulated in lung cancer. Sodium-glucose co-transporter-2 [SGLT2, also known as solute carrier family 5 member 2 (SLC5A2)] is an oncogene that promotes tumorigenesis. In this study, we aimed to determine the role of miR‑296‑5p in lung cancer and whether this involves the targeting of SGLT2. For this purpose, we examined miR‑296‑5p and SGLT2 expression in human lung cancer samples and cell lines by RT-qPCR and western blot analysis. In addition, the data analysis website TCGA was used for survival analysis with respect to SGLT2 expression. The effects of miR‑296‑5p were also examined on cell proliferation and cell cycle progression using respective assays. The results demonstrate that miR‑296‑5p is significantly downregulated in NSCLC tissues. Additionally, it is demonstrated that SGLT2 is directly targeted by miR‑296‑5p. Furthermore, our data reveal that the knockdown of SGLT2 using siRNA inhibits cell proliferation and impedes cell cycle progression. Collectively, data suggest that miR‑296‑5p not only inhibits NSCLC by downregulating SGLT2 expression, but also acts as a novel regulator of aberrant lung cancer cells to limit lung cancer progression.
非小细胞肺癌（NSCLC）是全球最常见的癌症类型之一，在中国的死亡率最高。微小RNA（miRNA或miR）参与肿瘤发生，其在癌症中的重要作用日益明显。特别是miR-296-5p的表达已被证明在肺癌中显著下调。钠-葡萄糖协同转运蛋白2 [SGLT2，也称为溶质载体家族5成员2（SLC5A2）]是一种促进肿瘤发生的癌基因。在本研究中，我们旨在确定miR-296-5p在肺癌中的作用，以及这是否涉及对SGLT2的靶向作用。为此，我们通过RT-qPCR和蛋白质印迹分析检测了人肺癌样本和细胞系中miR-296-5p和SGLT2的表达。此外，数据分析网站TCGA用于对SGLT2表达进行生存分析。还使用各自的检测方法研究了miR-296-5p对细胞增殖和细胞周期进程的影响。结果表明，miR-296-5p在NSCLC组织中显著下调。此外，证明SGLT2是miR-296-5p的直接靶点。此外，我们的数据显示，使用siRNA敲低SGLT2可抑制细胞增殖并阻碍细胞周期进程。总体而言，数据表明miR-296-5p不仅通过下调SGLT2表达来抑制NSCLC，还作为异常肺癌细胞的新型调节因子来限制肺癌进展。
