MicroRNA-138-5p targets the NFIB-Snail1 axis to inhibit colorectal cancer cell migration and chemoresistance
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Cancer Cell International Open Access
PRIMARY RESEARCH
MicroRNA-138-5p targets the NFIB-Snail1 axis to inhibit colorectal cancer cell migration and chemoresistance Weifeng Xu1, Beibei Chen1, Dianshan Ke2* and Xiaobing Chen1*
Abstract Background: Colorectal cancer ranks among the most lethal diseases worldwide. Although much progress has been made in research and treatment of colorectal cancer in recent years, the underlying mechanisms related to migration of the cancer cells and the reason for chemoresistance still remain unclear. In this research, we explored the underlying effect of miR-138-5p in colorectal cancer. Methods: We used qRT-PCR to investigate the expression of miR-138-5p, Snail1, NFIB in colorectal cancer cells. Lentiviral vectors containing miR-138-5p mimics and inhibitors were constructed and transfected cells. Wound healing assay was applied to illustrate interferences on cell migration. Fluorouracial, doxorubicin, cisplat in were used to detect chemotherapy resistance. In order to identify target genes, bioinformatic methods were applied. Snail1 and NFIB protein expression in stable cell lines was detected using Western blot. Double luciferase and CHIP experiment were used to verify binding sites. We used rescue experiments to further explore the interactions among Snail1, NFIB and miR-138-5p. Results: The expression of miR-138-5p in colorectal cancer cells was low. miR-138-5p inhibited cell migration in colorectal cancer, and could negatively regulate chemotherapy resistance. miR-138-5p targeted NFIB, and regulated Snail1 expression, which mediated colorectal cancer cell migration and chemotherapy resistance. Conclusions: Our research indicates that miR-138-5p could be a crucial modulator controlling colorectal cancer cell migration and chemoresistance, by acting upon the NFIB-Snail1 axis. miR-138-5p has an emerging prospect to be exploited as a new target for colorectal cancer. Keywords: Colorectal carcinoma, NFIB-Snail1, Migration, Chemoresistance, miR-138-5p Background Cancer is in the forefront of threatening the public health globally [1]. Colorectal carcinoma ranks the fourth among the most lethal types. Smoking, alcohol, lack of exercise, and overweight are contributing factors to the *Correspondence: [email protected]; [email protected] 1 Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University, 127 Dong Ming Road, Zhengzhou 450008, Henan, Peoples’ Republic of China 2 Department of Cell Biology, Southern Medical University, 510515 Guangzhou, Guangdong, China
genesis and poor prognosis of colorectal cancer. Its morbidity and mortality can be mitigated through proper screening and surveillance [2]. Treatments for colorectal cancer include endoscopic and surgical procedures, chemotherapy and radiotherapy [3]. Colonic stenting is also a palliative therapy for unresectable colon cancer [4]. In order to find better treatment options, it is increasingly important to discover novel molecular targets and mechanisms for colorectal cancer. miRNAs could modul
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