Abstract

MicroRNAs (miRNAs) play a critical role in regulation of numerous biological processes and pathogenesis of a variety of diseases. In addition, miRNAs contribute to carcinogenesis by acting as oncogenic or tumor suppressive. Circulating miRNAs including miR-150-5p are associated with colorectal cancer progression, and the putative targets of miR-150-5p include tumor suppressor gene, TP53. Here we sought to investigate the role of miR-150-5p-TP53 signaling pathway in proliferation of colon cancer and to determine expression levels of miR-miR-150-5p and TP53 in colon adenocarcinoma and adjacent non-cancerous tissue samples, or in human colon adenocarcinoma cell lines. MTT assay was used to determine proliferation and apoptosis in cell lines. Furthermore, we used Western blot to determine levels of cell cycle regulators with anti-miR-150-5p or apoptosis with overexpression of TP53. Our results show that expression levels of miR-150-5p were significantly elevated in clinical specimens from cancer patients. We further showed that inhibition of miR-150-5p increased TP53, and in turn, suppression of proliferation of colon adenocarcinoma. Moreover, inhibition of miR-150-5p or overexpression of TP53 caused cell arrest or apoptosis in colon adenocarcinoma. Our results support that miR-150-5p-TP53 pathway plays an important role in regulation of proliferation, cell arrest, and apoptosis in colon cancer, and could be an attractive target for therapy.

Highlights

  • Colorectal cancer (CRC) is a common malignant tumor with an incidence rate of a million people worldwide every year, and a major cause of mortality and morbidity in developed countries[1,2,3]

  • We sought to investigate the role of miR-150-5p-TP53 signaling in CRC, and we demonstrate that such a signaling plays a critical role in proliferation and progression of CRC

  • To validate a direct interaction between miR-150-5p and TP53, we cloned a miR-150-5p target site at 3′-UTR of TP53 mRNA upstream of firefly luciferase (FL) reporter gene, so that it could be regulated by miR-150-5p

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Summary

All Colon Adenocarcinomas

Activated, and such an activation of p53 can either transactivate or repress downstream target genes that in turn regulate cell cycle arrest, apoptosis, DNA repair, and angiogenesis and even metastasis[17]. Multiple studies have revealed the potential tumor-suppressive effect of TP53 in human tumor, the molecular function of TP53 in CRC has remained further defined. Expression of miR-150-5p has been linked with TP53-downstream target genes[15]. A preliminary bioinformatics analysis indicates that TP53 is a potential target of miR-150-5p18. We sought to investigate the role of miR-150-5p-TP53 signaling in CRC, and we demonstrate that such a signaling plays a critical role in proliferation and progression of CRC

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