Abstract
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.
Highlights
Colorectal cancer (CRC) is one of the most common malignancies in the world [1]
We measured TINCR expression levels in colorectal cancer (CRC) tissue samples and matched adjacent normal tissues (ANTs), and the results showed that TINCR expression was markedly higher in CRC tissue samples than that in the ANTs (Fig. 1B)
We analyze the relationship between TINCR expression and clinicopathological characteristics of CRC patients, and total 80 CRC cases were divided into low-expressing group (n=40) and high-expressing group (n=40) based on median value of TINCR expression
Summary
Colorectal cancer (CRC) is one of the most common malignancies in the world [1]. Despite improvement in medical technology over the past years, including surgical resection, chemotherapy, radiotherapy and molecular targeted therapy, the five-year survival rate of CRC still remains unsatisfied [1, 2]. Accumulating studies reported that many lncRNAs were dysregulated and involved in various biological process, such as cell proliferation, apoptosis, migration, invasion and metastasis [4, 5]. TINCR, a lncRNA about 3.7kb, controls human epidermal differentiation and is frequently deleted and downregulated in human squamous cell carcinoma (SCC) [6, 7]. Xiaochun Liu, et al [9] reported that TINCR was downregulated and suppressed cell proliferation and invasion via regulating miR-544a/FBXW7 axis in lung cancer. These prompted us to investigate the role of TINCR in human CRC
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