Zhao Weigang, Chen Tangbing, Zhao Yonghong
Department of Thoracic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200030, People's Republic of China.
Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, People's Republic of China.
Onco Targets Ther. 2020 Jun 24;13:6027-6036. doi: 10.2147/OTT.S249973. eCollection 2020.
Non-small cell lung cancer (NSCLC) is a deadly cancer type worldwide and the main sub-type of lung cancer. Cancer susceptibility candidate-9 (CASC9) was reported to be a key player in cancer progression. However, its function and underlying mechanism in NSCLC remain unclear.
Expression level of CASC9 in NSCLC tissues and cells was measured with RT-qPCR. Biological roles of CASC9 in NSCLC were analyzed with a series of in vitro experiments. Potential mechanisms of CASC9 in NSCLC were analyzed by predicting and validating the possible targets of CASC9 in NSCLC.
In this study, we found CASC9 expression was upregulated in NSCLC tissues and cell lines. High CASC9 expression was identified as a predictor for poorer overall survival of NSCLC patients. Furthermore, functional assays showed CASC9 knockdown suppressed NSCLC cell proliferation, migration, and invasion, while CASC9 overexpression caused opposite effects. We also found microRNA-335-3p (miR-335-3p) could act as a target of CASC9 in NSCLC and the inhibition effect of CASC9 knockdown on NSCLC progression required the activity of miR-335-3p. In addition, we identified S100 calcium-binding protein A14 (S100A14) acts as a target of miR-335-3p.
Taken together, our study suggested CASC9 could promote NSCLC progression via miR-335-3p/S100A14 axis. The CASC9/miR-335-3p/S100A14 regulatory triplets identified in this work might provide new therapeutic strategies for NSCLC treatment.
非小细胞肺癌(NSCLC)是全球范围内一种致命的癌症类型,也是肺癌的主要亚型。据报道,癌症易感性候选基因9(CASC9)是癌症进展中的关键因素。然而,其在NSCLC中的功能及潜在机制仍不清楚。
采用RT-qPCR检测NSCLC组织和细胞中CASC9的表达水平。通过一系列体外实验分析CASC9在NSCLC中的生物学作用。通过预测和验证CASC9在NSCLC中的可能靶点,分析其潜在机制。
在本研究中,我们发现NSCLC组织和细胞系中CASC9表达上调。高CASC9表达被确定为NSCLC患者总生存期较差的一个预测指标。此外,功能分析表明,敲低CASC9可抑制NSCLC细胞的增殖、迁移和侵袭,而CASC9过表达则产生相反的效果。我们还发现,微小RNA-335-3p(miR-335-3p)可作为NSCLC中CASC9的靶点,敲低CASC9对NSCLC进展的抑制作用需要miR-335-3p的活性。此外,我们确定S100钙结合蛋白A14(S100A14)是miR-335-3p的靶点。
综上所述,我们的研究表明CASC9可通过miR-335-3p/S100A14轴促进NSCLC进展。本研究中确定的CASC9/miR-335-3p/S100A14调控三联体可能为NSCLC治疗提供新的治疗策略。