Suppression of Capn4 by microRNA-1271 impedes the proliferation and invasion of colorectal cancer cells

被引:23
作者
Li, Jibin [1 ]
Xu, Jian [1 ]
Yan, Xiaofei [1 ]
Jin, Keer [1 ]
Li, Wenya [1 ]
Zhang, Rui [1 ]
机构
[1] China Med Univ, Liaoning Canc Hosp & Inst, Canc Hosp, Dept Colorectal Surg, 44 Xiaoheyan Rd, Shenyang 110042, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
Capn4; Colorectal cancer; miR-1271; Wnt; SMALL-SUBUNIT GENE; GASTRIC-CANCER; CISPLATIN RESISTANCE; MIR-124; SUPPRESSES; CALPAIN; CARCINOMA; GROWTH; METASTASIS; EXPRESSION; MIGRATION;
D O I
10.1016/j.biopha.2017.12.107
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Accumulating evidence has suggested that calpain small subunit 1 (Capn4) plays an important role in the development and progression of malignant tumors. However, little is known about the role of Capn4 in colorectal cancer (CRC). In this study, we aimed to investigate the potential role of Capn4 in CRC and the regulation of Capn4 by microRNAs (miRNAs). Here, we found that Capn4 expression was highly up-regulated in CRC cell lines. Knockdown of Capn4 by siRNA significantly inhibited the proliferation and invasion of CRC cell lines. Furthermore, knockdown of Capn4 suppressed Wnt signaling in CRC cells. Interestingly, Capn4 was found to be a target gene of miR-1271, a tumor suppressive miRNA. The results showed that miR-1271 negatively regulated Capn4 expression in CRC cells. An inverse correlation between miR-1271 and Capn4 was also shown in CRC clinical tissues. Moreover, the overexpression of miR-1271 suppressed the proliferation, invasion and Wnt signaling of CRC cells. Importantly, we found that the restoration of Capn4 expression significantly reversed the antitumor effects of miR-1271 in CRC cells. Overall, these results suggest that miR-1271 inhibits the proliferation and invasion of CRC cells by down-regulating Capn4. Our study suggests that Capn4 and miR-1271 may serve as potential therapeutic targets for the treatment of CRC.
引用
收藏
页码:162 / 168
页数:7
相关论文
共 36 条
[1]   Disruption of the murine calpain small subunit gene, Capn4:: Calpain is essential for embryonic development but not for cell growth and division [J].
Arthur, JSC ;
Elce, JS ;
Hegadorn, C ;
Williams, K ;
Greer, PA .
MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (12) :4474-4481
[2]   Capn4 Overexpression Underlies Tumor Invasion and Metastasis After Liver Transplantation for Hepatocellular Carcinoma [J].
Bai, Dou-Sheng ;
Dai, Zhi ;
Zhou, Jian ;
Liu, Yin-Kun ;
Qiu, Shuang-Jian ;
Tan, Chang-Jun ;
Shi, Ying-Hong ;
Huang, Cheng ;
Wang, Zheng ;
He, Yi-Feng ;
Fan, Jia .
HEPATOLOGY, 2009, 49 (02) :460-470
[3]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[4]   Colorectal cancer [J].
Brenner, Hermann ;
Kloor, Matthias ;
Pox, Christian Peter .
LANCET, 2014, 383 (9927) :1490-1502
[5]   miR-124 suppresses the migration and invasion of glioma cells in vitro via Capn4 [J].
Cai, Jia-Jun ;
Qi, Zeng-Xin ;
Chen, Ling-Chao ;
Yao, Yu ;
Gong, Yan ;
Mao, Ying .
ONCOLOGY REPORTS, 2016, 35 (01) :284-290
[6]   Increased Expression of Capn4 is Associated with the Malignancy of Human Glioma [J].
Cai, Jia-Jun ;
Qi, Zeng-Xin ;
Hua, Wei ;
Zhu, Jing-Jing ;
Zhang, Xin ;
Yao, Yu ;
Mao, Ying .
CNS NEUROSCIENCE & THERAPEUTICS, 2014, 20 (06) :521-527
[7]   Capn4 contributes to tumour growth and metastasis of hepatocellular carcinoma by activation of the FAK-Src signalling pathways [J].
Dai, Zhi ;
Zhou, Shao-Lai ;
Zhou, Zheng-Jun ;
Bai, Dou-Sheng ;
Xu, Xiao-Yu ;
Fu, Xiu-Tao ;
Chen, Qing ;
Zhao, Yi-Ming ;
Zhu, Kai ;
Yu, Lei ;
Yang, Guo-Huan ;
Wang, Zheng ;
Wu, Wei-Zhong ;
Zhou, Jian ;
Fan, Jia .
JOURNAL OF PATHOLOGY, 2014, 234 (03) :316-328
[8]   Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions [J].
De Sousa E Melo, Felipe ;
Wang, Xin ;
Jansen, Marnix ;
Fessler, Evelyn ;
Trinh, Anne ;
de Rooij, Laura P. M. H. ;
de Jong, Joan H. ;
de Boer, Onno J. ;
van Leersum, Ronald ;
Bijlsma, Maarten F. ;
Rodermond, Hans ;
van der Heijden, Maartje ;
van Noesel, Carel J. M. ;
Tuynman, Jurriaan B. ;
Dekker, Evelien ;
Markowetz, Florian ;
Medema, Jan Paul ;
Vermeulen, Louis .
NATURE MEDICINE, 2013, 19 (05) :614-618
[9]   Reduced cell migration and disruption of the actin cytoskeleton in calpain-deficient embryonic fibroblasts [J].
Dourdin, N ;
Bhatt, AK ;
Dutt, P ;
Greer, PA ;
Arthur, JSC ;
Elce, JS ;
Huttenlocher, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (51) :48382-48388
[10]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269