MiR-760 suppresses human colorectal cancer growth by targeting BATF3/AP-1/cyclinD1 signaling

Ling Cao,Weitang Yuan,Jinbo Liu,Qun Gao,Dan Wang,Feng Li,Chaoqi Zhang,Zhibo Shen,Yulin Liu,Yi Zhang,Lan Huang

doi:10.1186/s13046-018-0757-8

Abstract

BackgroundRecent studies have reported that microRNAs (miRNAs) often function as negative post-transcriptional regulators with altered expression levels found in colorectal cancer (CRC). There have been few studies on miRNAs that regulate the oncogenic alterations in CRC. Here, we aim to explore the anti-cancer miRNA and the potential mechanisms by which miRNAs modulate CRC progression.MethodsWe performed an integrated analysis of CRC miRNA expression datasets in The Cancer Genome Atlas (TCGA). The miRNA with the lowest expression, miR-760, was validated in an independent validation sample cohort of 76 CRC tissues. Functional assays, such as CCK-8 assay, colony formation assay, and CFSE staining, were used to determine the oncogenic role of miR-760 in human CRC progression. Furthermore, western blotting and dual-luciferase reporter assay were used to determine the mechanism by which miR-760 promotes proliferation of CRC cells. Xenograft nude mouse models were used to determine the role of miR-760 in CRC tumorigenicity in vivo. Immunohistochemical assays were conducted to study the relationship between miR-760 expression and basic leucine zipper transcriptional factor ATF-like 3 (BATF3) expression in human CRC samples.ResultsmiR-760 was markedly downregulated in CRC tissues, and low miR-760 expression was associated with poor prognosis among CRC patients. Upregulation of miR-760 suppressed CRC cell proliferation, whereas downregulation of miR-760 promoted CRC proliferation in vitro. Additionally, we identified BATF3 as a direct target of miR-760, and that the essential biological function of miR-760 during CRC progression both in vitro and in vivo is to suppress the expression of BATF3 and downstream cyclinD1 via AP-1 transcription factor. Finally, we showed a significant correlation between miR-760 and BATF3 expression in CRC tissues.ConclusionsmiR-760 inhibited CRC growth by downregulating BATF3/AP-1/ cyclinD1 signaling.

Highlights

Recent studies have reported that microRNAs often function as negative post-transcriptional regulators with altered expression levels found in colorectal cancer (CRC)
Our present study suggests that miR-760 suppresses cell proliferation and tumorigenicity in Colorectal cancer (CRC) cells by targeting basic leucine zipper transcriptional factor ATF-like 3 (BATF3) mRNA and suppressing the expression of BATF3 and downstream cyclin D1
Low miR-760 expression was observed in CRC tissues and was associated with poor prognosis It has been demonstrated that miRNAs are key regulators of many cellular processes such as development, differentiation, apoptosis, and proliferation, and that several miRNAs can cooperatively induce cellular senescence and apoptosis in colorectal cancer [26]

Summary

Introduction

Recent studies have reported that microRNAs (miRNAs) often function as negative post-transcriptional regulators with altered expression levels found in colorectal cancer (CRC). There have been few studies on miRNAs that regulate the oncogenic alterations in CRC. We aim to explore the anti-cancer miRNA and the potential mechanisms by which miRNAs modulate CRC progression. MicroRNAs (miRNAs) are small noncoding RNA molecules that modulate the expression of target mRNAs at a posttranscriptional level [3]. They regulate critical aspects of the oncogenic phenotype through the disruption of protein translation by selective binding and degradation of target mRNAs [4]. There have been few studies examining miRNAs that regulate the oncogenic mutations in CRC

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