Dataset Information

The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1.

ABSTRACT: We previously discovered that rs7911488T>C in pre-miR-1307 was closely correlated to the risk of colorectal cancer (CRC). However, the roles of rs7911488 in CRC are still largely unknown. Here we explored the roles of rs7911488 in the growth and metastasis of CRC. We firstly generated cell lines SW480-T and SW480-C for stable expression of rs7911488 T-allelic and C-allelic pre-miR-1307, respectively. We subcutaneously grafted the cells into nude mice. We found that SW480-T tumors with high expression of miR-1307 obviously grew faster than the SW480-C tumors. Moreover, liver metastases (5/8) were observed in the mice bearing SW480-T tumors but not the SW480-C tumor-bearing mice. The results from colony formation assays, transwell assays, and wound healing assays demonstrated that the proliferative and metastatic abilities of SW480-T cells were evidently more potent than the SW480-C cells. Then we utilized gene array, real-time PCR, western blotting, and dual-luciferase reporter assays to figure out that miR-1307 directly inhibited PPRX1 expression by binding to its 3'-UTR. Thereafter, we confirmed that the proliferative and metastatic abilities of SW480 and HCT-116 cells were markedly enhanced by miR-1307, but were suppressed by PRRX1. Moreover, the regulatory roles of miR-1307 in the proliferation and metastasis of CRC cells were reversed by PRRX1. Notably, we also found that PRRX1 repressed CRC tumor growth in nude mice. In summary, our current study revealed that rs7911488-T allele led to over-expression of miR-1307, which inhibited PRRX1 and consequently promoted the proliferation and migration of CRC cells. This might offer a novel insight into the progression of CRC.

SUBMITTER: Yang M

PROVIDER: S-EPMC7434880 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1.

Yang Man M Liu Xinchang X Meng Fanyi F Zhang Yawen Y Wang Mengmeng M Chen Yinshuang Y Guo Xuqin X Chen Weichang W Wang Weipeng W

Cell death & disease 20200807 8

We previously discovered that rs7911488T>C in pre-miR-1307 was closely correlated to the risk of colorectal cancer (CRC). However, the roles of rs7911488 in CRC are still largely unknown. Here we explored the roles of rs7911488 in the growth and metastasis of CRC. We firstly generated cell lines SW480-T and SW480-C for stable expression of rs7911488 T-allelic and C-allelic pre-miR-1307, respectively. We subcutaneously grafted the cells into nude mice. We found that SW480-T tumors with high expre ...[more]

PMID: 32811812

Similar Datasets

Project description:Mounting evidences indicate that circular RNAs (circRNAs) have a vital role in human diseases, especially cancers. More recently, circHIPK3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, its role in colorectal cancer (CRC) has not been explored. In this study, we found circHIPK3 was significantly upregulated in CRC tissues and cell lines, at least in part, due to c-Myb overexpression and positively correlated with metastasis and advanced clinical stage. Moreover, Cox multivariate survival analysis showed that high-level expression of circHIPK3 was an independent prognostic factor of poor overall survival (OS) in CRC (hazard ratio [HR] = 2.75, 95% confidence interval [CI] 1.74-6.51, p = 0.009). Functionally, knockdown of circHIPK3 markedly inhibited CRC cells proliferation, migration, invasion, and induced apoptosis in vitro and suppressed CRC growth and metastasis in vivo. Mechanistically, by using biotinylated-circHIPK3 probe to perform RNA pull-down assay in CRC cells, we identified miR-7 was the only one microRNA that was abundantly pulled down by circHIPK3 in both HCT116 and HT29 cells and these interactions were also confirmed by biotinylated miR-7 pull-down and dual-luciferase reporter assays. Overexpression of miR-7 mimicked the effect of circHIPK3 knockdown on CRC cells proliferation, migration, invasion, and apoptosis. Furthermore, ectopic expression of circHIPK3 effectively reversed miR-7-induced attenuation of malignant phenotypes of CRC cells by increasing the expression levels of miR-7 targeting proto-oncogenes (FAK, IGF1R, EGFR, YY1). Remarkably, the combination of circHIPK3 silencing and miR-7 overexpression gave a better effect on tumor suppression both in vitro and in vivo than did circHIPK3 knockdown or miR-7 overexpression alone. Taken together, our data indicate that circHIPK3 may have considerable potential as a prognostic biomarker in CRC, and support the notion that therapeutic targeting of the c-Myb/circHIPK3/miR-7 axis may be a promising treatment approach for CRC patients.

Dataset Information

The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1.

Publications

The rs7911488-T allele promotes the growth and metastasis of colorectal cancer through modulating miR-1307/PRRX1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets