miR-34a Regulates Expression of the Stathmin-1 Oncoprotein and Prostate Cancer Progression

• Published in: Molecular cancer research 2018-07, Vol.16 (7), p.1125-1137
• Main Authors: Chakravarthi, Balabhadrapatruni V S K, Chandrashekar, Darshan S, Agarwal, Sumit, Balasubramanya, Sai Akshaya Hodigere, Pathi, Satya S, Goswami, Moloy T, Jing, Xiaojun, Wang, Rui, Mehra, Rohit, Asangani, Irfan A, Chinnaiyan, Arul M, Manne, Upender, Sonpavde, Guru, Netto, George J, Gordetsky, Jennifer, Varambally, Sooryanarayana
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Alcohol Oxidoreductases - genetics; Animals; Cancer; Cell Line, Tumor; Cell Movement - genetics; Cell proliferation; Cell Proliferation - genetics; Disease Progression; DNA-Binding Proteins - genetics; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Growth Differentiation Factor 15 - genetics; Humans; Male; Metastases; Metastasis; Mice; MicroRNAs - genetics; Molecular chains; Oncoprotein 18; Oncoproteins; Prostate - metabolism; Prostate - pathology; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Proteins; Ribonucleic acid; RNA; Stathmin; Stathmin - genetics; Therapeutic applications; Transcription; Tumor suppressor genes; Tumorigenesis; Tumors; Xenograft Model Antitumor Assays
• ISSN: 1541-7786; 1557-3125
• DOI: 10.1158/1541-7786.MCR-17-0230

In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1 and oncoprotein 18) is often overexpressed. STMN1 is involved in various cellular processes, including cell proliferation, motility, and tumor metastasis. Here, it was found that the expression of STMN1 RNA and protein is elevated in metastatic prostate cancers. Knockdown of STMN1 resulted in reduced proliferation and invasion of cells and tumor growth and metastasis Furthermore, miR-34a downregulated STMN1 by directly binding to its 3'-UTR. Overexpression of miR-34a in prostate cancer cells reduced proliferation and colony formation, suggesting that it is a tumor suppressor. The transcriptional corepressor C-terminal binding protein 1 (CtBP1) negatively regulated expression of miR-34a. Furthermore, gene expression profiling of STMN1-modulated prostate cancer cells revealed molecular alterations, including elevated expression of growth differentiation factor 15 (GDF15), which is involved in cancer progression and potentially in STMN1-mediated oncogenesis. Thus, in prostate cancer, CtBP1-regulated miR-34a modulates STMN1 expression and is involved in cancer progression through the CtBP1\miR-34a\STMN1\GDF15 axis. The CtBP1\miR-34a\STMN1\GDF15 axis is a potential therapeutic target for treatment of aggressive prostate cancer. .