Knockdown of linc-UFC1 suppresses proliferation and induces apoptosis of colorectal cancer.

T Yu,X-J Lu,C-Z Huang,J-H Xu,H Ouyang,W Zhong,T-D Shan,S-Y Wang,J-Y Li,Q-K Chen

doi:10.1038/cddis.2016.124

Abstract

Long intergenic noncoding RNAs (lincRNAs) have important roles in biological functions, molecular mechanisms and prognostic values in colorectal cancer (CRC). In this context, the roles of linc-UFC1 remain to be elucidated. In this study, linc-UFC1 was overexpressed in CRC patient tissues and positively correlated with tumor grade, N stage and M stage. Inhibition of linc-UFC1 resulted in cell proliferation inhibition and G1 cell cycle arrest, which was mediated by cyclin D1, CDK4, Rb and phosphorylated Rb. In addition, inhibition of linc-UFC1 induced cell apoptosis through the intrinsic apoptosis signaling pathway, as evidenced by the activation of caspase-9 and caspase-3. An investigation of the signaling pathway revealed that the effects on proliferation and apoptosis following linc-UFC1 knockdown were mediated by suppression of β-catenin and activation of phosphorylated P38. Furthermore, the P38 inhibitor SB203580 could attenuate the apoptotic effect achieved by linc-UFC1 knockdown, confirming the involvement of P38 signaling in the induced apoptosis. Taken together, linc-UFC1 might have a critical role in pro-proliferation and anti-apoptosis in CRC by regulating the cell cycle, intrinsic apoptosis, and β-catenin and P38 signaling. Thus, linc-UFC1 could be a potential therapeutic target and novel molecular biomarker for CRC.

Highlights

In recent years, growing evidence has suggested that epigenetic alterations have a significant role in carcinogenesis and the progression of malignancies.[4,5] Long noncoding RNAs, a subgroup of noncoding RNAs, are nonprotein-coding transcripts with a length 4200 nucleotides.[6,7] Based on their structural or functional characteristics, lncRNAs can be classified further into several subgroups, including natural antisense, transcripts, circular RNAs, pseudogenes and long intergenic noncoding RNAs.[8]
We identified a novel lincRNA, termed lincUFC1, and we showed that altered linc-UFC1 expression could interact with the mRNA-stabilizing protein HuR to increase levels of β-catenin in hepatocellular carcinoma (HCC) cells.[16]
The expression level of linc-UFC1 was assessed in 65 paired Colorectal cancer (CRC) samples and histologically normal adjacent tissues by real-time quantitative polymerase chain reaction (QPCR), which was normalized to GAPDH

Summary

Introduction

In recent years, growing evidence has suggested that epigenetic alterations have a significant role in carcinogenesis and the progression of malignancies.[4,5] Long noncoding RNAs (lncRNAs), a subgroup of noncoding RNAs, are nonprotein-coding transcripts with a length 4200 nucleotides.[6,7] Based on their structural or functional characteristics, lncRNAs can be classified further into several subgroups, including natural antisense, transcripts, circular RNAs, pseudogenes and long intergenic noncoding RNAs (lincRNAs).[8]. The accumulation of genetic and epigenetic alterations mediates CRC formation and progression by deregulating key signaling pathways in cancer cells. We identified a novel lincRNA, termed lincUFC1, and we showed that altered linc-UFC1 expression could interact with the mRNA-stabilizing protein HuR to increase levels of β-catenin in hepatocellular carcinoma (HCC) cells.[16] Despite the above findings, linc-UFC1 expression has not been investigated in CRC. We investigated linc-UFC1 expression in CRC tissues and cancer cell lines. We determined that linc-UFC1 might have a Received 01.11.15; revised 21.3.16; accepted 11.4.16; Edited by G Calin critical role in promoting the tumorigenesis and progression of CRC through the regulation of proliferation and apoptosis

Methods

Results

Conclusion