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 7

SURC regulated CRC cell cycle by affecting CCND2 expression.

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SURC regulated CRC cell cycle by affecting CCND2 expression. (A) SURC-re...
(A) SURC-regulated gene expression by RNA-Seq. (B) qPCR shows the expression of CCND2 in LoVo and SW620 cells infected with lenti-shNC and lenti-shSURC (n = 3; **P < 0.01). (C) qPCR shows the expression of CCND2 in s.c. tumors of LoVo and SW620 cells (n = 3; **P < 0.01). (D) Western blotting shows the expression of CCND2 in LoVo and SW620 cells. GAPDH was used as a loading control. (E) IHC staining of CCND2 in the s.c. tumors of shNC and shSURC cells. Analysis of CCND2-positive cells (n = 3; **P < 0.01). (F) Dual-luciferase reporter assays to test the interaction between miR–185-5p and CCND2 by using a synthetic miR–185-5p mimic cotransfected with CCND2-wt or CCND2-mt constructs (n = 3; **P < 0.01). (G) Dual luciferase assay of SW620 cells cotransfected with the CCND2 reporter constructs (wt or mt), the SURC overexpressing plasmids and miR–185-5p mimic (n = 3; **P < 0.01). (H) The cell cycle was analyzed by flow cytometry analysis in SW620 cells (n = 3; **P < 0.01). (I) BrdU assays of the SW620 cells with SURC knockdown by shRNAs compared with the control. (Scale bar: 100 μm; n = 3; **P < 0.01). (J) IHC staining of Ki67 in the shNC and shSURC s.c. tumors. Scale bar: 100 μm. Analysis of Ki67-positive cells in each frame (n = 3; **P < 0.01). Data are shown as mean ± SEM. Differentially expressed mRNAs were defined when the fold change was greater than or equal to 1 and adjusted P value was less than 0.05 between different groups. Statistical differences were calculated using 1-way ANOVA and Dunnett’s multiple-comparison test (for B, C, E, and H–J) and unpaired 2-tailed Student’s t test (for F and G). mt, mutant.