Yu Shaojun, Wang Da, Shao Yingkuan, Zhang Teng, Xie Haiting, Jiang Xiaomeng, Deng Qun, Jiao Yurong, Yang Jinhua, Cai Cheng, Sun Lifeng
Surgical Oncology Department, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
Aging (Albany NY). 2019 Mar 10;11(5):1389-1403. doi: 10.18632/aging.101839.
Mounting evidences have indicated that long noncoding RNAs (lncRNAs) play pivotal roles in human diseases, especially in cancers. Recently, TINCR was proposed to be involved in tumor progression. However, its role in colorectal cancer (CRC) remains elusive. In our study, we found that SP1-induced TINCR was significantly upregulated in CRC tissues and cell lines. Moreover, cox multivariate survival analysis revealed that high TINCR was an independent predictor of poor overall survival (OS). Functionally, knockdown of TINCR obviously suppressed CRC cells proliferation, migration and invasion in vitro, and inhibited CRC cells growth and metastasis in vivo. Mechanistically, we identified TINCR could act as a miR-7-5p sponge using RNA pull down, luciferase reporter and RIP assays. Furthermore, we showed that TINCR might promote CRC progression via miR-7-5p-mediated PI3K/Akt/mTOR signaling pathway. Lastly, we revealed that plasma TINCR expression was upregulated in CRC when compared to healthy controls and could be a promising diagnostic biomarker for CRC. Based on above results, our data indicated that TINCR might serve as a potential diagnostic and prognostic biomarker for CRC.
越来越多的证据表明，长链非编码RNA（lncRNA）在人类疾病尤其是癌症中发挥着关键作用。最近，有研究提出TINCR参与肿瘤进展。然而，其在结直肠癌（CRC）中的作用仍不清楚。在我们的研究中，我们发现SP1诱导的TINCR在CRC组织和细胞系中显著上调。此外，多因素Cox生存分析显示，高表达的TINCR是总生存期（OS）较差的独立预测因素。在功能上，敲低TINCR明显抑制了CRC细胞在体外的增殖、迁移和侵袭，并在体内抑制了CRC细胞的生长和转移。机制上，我们通过RNA下拉、荧光素酶报告基因和RIP实验确定TINCR可以作为miR-7-5p的海绵。此外，我们发现TINCR可能通过miR-7-5p介导的PI3K/Akt/mTOR信号通路促进CRC进展。最后，我们发现与健康对照相比，CRC患者血浆中TINCR表达上调，并且可能是CRC一个有前景的诊断生物标志物。基于以上结果，我们的数据表明TINCR可能作为CRC潜在的诊断和预后生物标志物。
