miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma

Nan Kang; Yunwei Ou; Guangchao Wang; Jie Chen; Dan Li; Qimin Zhan

doi:10.7717/peerj.10020

miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma

PeerJ. 2021 Jan 5:9:e10020. doi: 10.7717/peerj.10020. eCollection 2021.

Authors

Nan Kang^{1

2}, Yunwei Ou¹, Guangchao Wang¹, Jie Chen³, Dan Li¹, Qimin Zhan^{1

3}

Affiliations

¹ State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
² Department of Pathology, Peking University People's Hospital, Beijing, China.
³ Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3'untranslated regions (3'UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently, transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13'UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 expression in ESCC.

Keywords: Down-regulate; SNP; miR-875-5p; CAPZA1; ESCC.

Grants and funding

This work was supported by the National Natural Science Foundation of China (NO.81830086 and 81988101), Beijing Nova Program (NO. xx2018040), CAMS Initiative for Innovative Medicine (NO.2017-I2M-3-004) and the Research and Development Funding of Peking University People’s Hospital (NO.RDY2018-08). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.