Overexpression of SOX4 induces up-regulation of miR-126 and miR-195 in LNCaP prostate cancer cell line

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ORIGINAL ARTICLE

Overexpression of SOX4 induces up-regulation of miR-126 and miR-195 in LNCaP prostate cancer cell line Nam Nhut Phan

. Carlos S. Moreno . Yu-Heng Lai

Received: 1 November 2019 / Accepted: 9 May 2020 Ó The Author(s) 2020

Abstract The present study aims to investigate the association between SOX4, Wnt signaling, and miRNAs under Wnt3 induction via bioinformatics analysis and functional essays. To briefly explore the expression of SOX4 protein in various types of cancer, we used ONCOMINE, a highly reputable cancer database, for comparison of its expression in prostate carcinoma relative to normal prostate gland. Concomitantly, we used CCLE to plot the copy number of SOX4 against its mRNA expression status in various cancerous cell lines to confirm the carcinogenesis role of SOX4. Afterward, whole profiling expression of microRNA in SOX4-stably expressed LNCaP cell line under the effect of Wnt3A were demonstrated. After identifying microRNA targets, STRING database and MIROB were used to explore the functional

N. N. Phan NTT Institute of Hi-Technology, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam C. S. Moreno Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia C. S. Moreno Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, Georgia Y.-H. Lai (&) Department of Chemistry, Chinese Culture University, Taipei 111, Taiwan e-mail: [email protected]

connection between proteins and microRNA with proteins. The results from our study shows that overexpressed of SOX4 was confirmed in both carcinogenesis tissue and cancer cell lines in Oncomine and CCLE database. In addition, five miRNAs, miR-16, miR-19a, miR320, miR-195, and miR-126, were differentially expressed in LNCaP cell line induced by Wnt3a. Pathway analysis of these targets proposed interaction networks of SOX4, Wnt3a with miR-126 and miR-195. Altogether, the miRNAs involved in Wnt and SOX4-mediated prostate cancer such as miR126 and miR-195 could be potential biomarkers in prostate cancer. Keywords MicroRNAs  Wnt pathway  Prognosis  Carcinogenesis  Biomarkers

Introduction Prostate cancer is the most common non-cutaneous neoplasm and second common cause of cancer other than skin cancer in American men. It has been estimated that there were over 174,652 new cases and 31,620 deaths in 2019, which is second leading cause of cancer death (Society 2019). One of the important challenges in current prostate cancer research is to develop effective methods to determine whether a patient is likely to progress to aggressive,

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Cytotechnology

metastatic disease after treatment (Frame and Cant 2015; Silberstein et al. 2013). The current gold standard for pathological evaluation of the status of prostate cancer patients is the Gleason score, which is calculated based on summing the grades of the glandular architecture of the two most prevalent histological components of the tumor (Maurice et al. 2016). Genera