MiRNA-29a as a tumor suppressor mediates PRIMA-1Met-induced anti-myeloma activity by targeting c-Myc.

Oncotarget
M N SahaH Chang

Abstract

The proto-oncogene c-Myc plays substantial role in multiple myeloma (MM) pathogenesis and is considered a potential drug target. Here we provide evidence of a novel mechanism for PRIMA-1Met, a small molecule with anti-tumor activity in phase I/II clinical trial, showing that PRIMA-1Met induces apoptosis in MM cells by suppressing c-Myc and upregulating miRNA-29a. Our study further demonstrates that miRNA-29a functions as a tumor suppressor which targets c-Myc. The baseline expression of miR-29a was significantly lower in MM cell lines and MM patient samples compared to normal hematopoietic cells. In addition, ectopic expression of miRNA-29a or exposure to PRIMA-1Met reduced cell proliferation and induced apoptosis in MM cells. On the other hand, overexpression of c-Myc at least partially reverted the inhibitory effects of PRIMA-1Met or miRNA-29a overexpression suggesting the miRNA-29a/c-Myc axis mediates anti-myeloma effects of PRIMA-1Met. Importantly, intratumor delivery of miRNA-29a mimics induced regression of tumors in mouse xenograft model of MM and this effect synergized with PRIMA-1Met. Our study indicates that miRNA-29a is a tumor suppressor that plays an important role during PRIMA-1Met-induced apoptotic signaling by t...Continue Reading

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Citations

Jan 19, 2019·Non-coding RNA·Irena Misiewicz-KrzeminskaNorma C Gutiérrez
Apr 24, 2020·Journal of Cellular Physiology·Jingwen LiYu Hu
Aug 6, 2016·Oncotarget·Jahangir AbdiHong Chang
Jul 31, 2016·Oncotarget·Lucia Di MarzoMaria Antonia Frassanito
May 21, 2019·Experimental and Therapeutic Medicine·Shifeng LongGuoan Chen
May 18, 2020·International Immunopharmacology·Gholamreza Rezaei DanbaranHamed Mohammadi
Jun 3, 2021·Cancers·Mélody CaillotBrigitte Sola
Nov 10, 2020·Life Sciences·Md Nazim Uddin, Xiaosheng Wang
Aug 28, 2021·Biomedicines·Ekaterina Mikhailovna StasevichAnton Markovich Schwartz

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Methods Mentioned

BETA
xenograft
PCR
transfection
Assay

Software Mentioned

MiRanda
SABiosciences
RT 2 Profiler PCR Array Data Analysis
CellQuest
GraphPad Prism

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis