Tumor Biology

, Volume 37, Issue 10, pp 13155–13166

Downregulation of HMGB1 by miR-34a is sufficient to suppress proliferation, migration and invasion of human cervical and colorectal cancer cells

  • Karthik Subramanian Chandrasekaran
  • Anusha Sathyanarayanan
  • Devarajan Karunagaran
Original Article

DOI: 10.1007/s13277-016-5261-1

Cite this article as:
Chandrasekaran, K.S., Sathyanarayanan, A. & Karunagaran, D. Tumor Biol. (2016) 37: 13155. doi:10.1007/s13277-016-5261-1

Abstract

High mobility group box 1 (HMGB1) is a ubiquitous nuclear protein known to be highly expressed in human cervical (CaCx) and colorectal (CRC) cancers, and sustained high levels of HMGB1 contribute to tumourigenesis and metastasis. HMGB1-targeted cancer therapy is of recent interest, and there are not many studies on miRNA-mediated HMGB1 regulation in these cancers. Since miRNA-based therapeutics for cancer is gaining importance in recent years, it was of interest to predict miRNAs targeting HMGB1. Based on the identification of a potential miR-34a response element in HMGB1–3′ untranslated region (3′UTR) and an inverse correlation between HMGB1 and miR-34a expression levels in CaCx and CRC tissues, from a subset of the local population as well as a large sampling from TCGA database, experiments were performed to validate HMGB1 as a direct target of miR-34a in CaCx and CRC cells. Ectopic expression of miR-34a decreased the wild-type HMGB1–3′UTR luciferase activity but not that of its mutant in 3′UTR luciferase assays. While forced expression of miR-34a in CaCx and CRC cells inhibited HMGB1 mRNA and protein levels, proliferation, migration and invasion, inhibition of endogenous miR-34a enhanced these tumourigenic properties. siRNA-mediated HMGB1 suppression imitated miR-34a expression in reducing proliferation and metastasis-related events. Combined with the disparity in expression of miR-34a and HMGB1 in clinical specimens, the current findings would help in not only understanding the complexity of miRNA-target regulatory mechanisms but also in designing novel therapeutic interventions in CaCx and CRC.

Keywords

microRNA-34a HMGB1 Human cervical cancer Human colorectal cancer Tumourigenicity 

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  1. 1.Department of Biotechnology, Bhupat and Jyoti Mehta School of BiosciencesIndian Institute of Technology MadrasChennaiIndia