A specific upregulated long noncoding RNA in colorectal cancer promotes cancer progression
Junshu Li, Yanhong Ji, Na Chen, Huiling Wang, Chao Fang, Xiaonan Yin, Zhiyuan Jiang, Zhexu Dong, Dan Zhu, Jiamei Fu, Wencheng Zhou, Ruiyi Jiang, Ling He, Zhang Hantao, Gang Shi, Lin Cheng, Xiaolan Su, Lei Dai, Hongxin Deng
Junshu Li, Yanhong Ji, Na Chen, Huiling Wang, Chao Fang, Xiaonan Yin, Zhiyuan Jiang, Zhexu Dong, Dan Zhu, Jiamei Fu, Wencheng Zhou, Ruiyi Jiang, Ling He, Zhang Hantao, Gang Shi, Lin Cheng, Xiaolan Su, Lei Dai, Hongxin Deng
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Research Article Cell biology Gastroenterology

A specific upregulated long noncoding RNA in colorectal cancer promotes cancer progression

Abstract

Long noncoding RNA (lncRNA) plays a crucial role in the pathogenesis of various diseases, including colorectal cancer (CRC). The gene mutations of adenomatous polyposis coli (APC) were found in most patients with CRC. They function as important inducers of tumorigenesis. Based on our microarray results, we identified a specific upregulated lncRNA in CRC (SURC). Further analysis showed that high SURC expression correlated with poorer disease-free survival and overall survival in patients with CRC. Furthermore, we found that mutated APC genes can promote the transcription of SURC by reducing the degradation of β-catenin protein in CRC. Functional assays revealed that knockdown of SURC impaired CRC cell proliferation, colony formation, cell cycle, and tumor growth. Additionally, SURC promotes CCND2 expression by inhibiting the expression of miR–185-5p in CRC cells. In conclusion, we demonstrate that SURC is a specific upregulated lncRNA in CRC and the SURC/miR–185-5p/CCND2 axis may be targetable for CRC diagnosis and therapy.

Authors

Junshu Li, Yanhong Ji, Na Chen, Huiling Wang, Chao Fang, Xiaonan Yin, Zhiyuan Jiang, Zhexu Dong, Dan Zhu, Jiamei Fu, Wencheng Zhou, Ruiyi Jiang, Ling He, Zhang Hantao, Gang Shi, Lin Cheng, Xiaolan Su, Lei Dai, Hongxin Deng

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Figure 5

Direct binding of SURC to miR–185-5p.

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Direct binding of SURC to miR–185-5p. (A) CCK8 assay shows the relative ...
(A) CCK8 assay shows the relative cell growth in SW620 cells transfected with siNC or siDicer (n = 5; **P < 0.01). (B) Colony formation of SW620 cells transfected with siNC or siDicer (n = 3; **P < 0.01). (C) Altered microRNA expression in shSURC or shNC-treated LoVo cells by RNA-Seq. (D) ChIRP assay detected the ability of SURC direct binding to miRNA in SW620 cells (n = 3; **P < 0.01). (E) FISH assay shows the colocalization of SURC and miR–185-5p. Scale bar: 10 μm. (F) Prediction of binding sites of SURC and miR–185-5p by bioinformatics analysis. (G) The dual-luciferase reporter system confirmed 2085-2521 segment of SURC was combined with miR–185-5p (n = 3; **P < 0.01). (H) The dual-luciferase reporter system shows the combination between miR–185-5p and SURC core region transfected with SURC2085-2521WT or MUT plasmid (n = 3; **P < 0.01). (I) Colony formation shows the function of SURC core region in RKO cells which was transfected with SURC2085-2521WT or MUT plasmid (n = 3; **P < 0.01). (J) Tumor volume and (K) tumor weight were measured in RKO cells infected with SURC2085-2521 MUT compared with WT cells (n = 7; **P < 0.01). Data are shown as the mean ± SEM. Differentially expressed miRNAs were defined when the fold change was greater than or equal to 1 and adjusted P value less than 0.05 between different groups. Statistical differences were calculated using 1-way ANOVA and Dunnett’s multiple-comparison test (for A, B, D, and I–K) and unpaired 2-tailed Student’s t test (for G and H).