MiR-19b suppresses PTPRG to promote breast tumorigenesis.

Minghui Liu,Rong Yang,Xin Yan,Shufang Cui,Hongwei Liang,Yeting Hong,Chao Ye,Yuanyuan Gu,Yanqing Liu,Xi Chen,Liang Yan,Uzair Urrehman,Chen-Yu Zhang,Chihao Zhao

doi:10.18632/oncotarget.11799

Abstract

Protein tyrosine phosphatase receptor type G (PTPRG) is an important tumor suppressor gene in multiple human cancers. In this study, we found that PTPRG protein levels were downregulated in breast cancer tissues while the mRNA levels varied irregularly, implying a post-transcriptional mechanism was involved. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatics analysis to search for microRNAs that potentially targets PTPRG in the setting of breast cancer. We identified two specific binding sites for miR-19b in the 3′-untranslated region of PTPRG. We further identified an inverse correlation between miR-19b and PTPRG protein levels, but not mRNA levels, in human breast cancer tissues. By overexpressing or knocking down miR-19b in MCF-7 cells and MDA-231 cells, we experimentally confirmed that miR-19b directly suppresses PTPRG expression. Furthermore, we determined that the inhibition of PTPRG by miR-19b leads to increased proliferation, stimulated cell migration and reduced apoptosis. Taken together, our findings provide the first evidence that miR-19b inhibits PTPRG expression to promote tumorigenesis in human breast cancer.

Highlights

Breast cancer is the most commonly diagnosed invasive cancer worldwide and the second leading cause of cancer death among women
We further identified an inverse correlation between miR-19b and phosphatase receptor type G (PTPRG) protein levels, but not mRNA levels, in human breast cancer tissues
After measuring the protein levels of PTPRG in 14 paired breast cancer tissues and their corresponding noncancerous tissues, we observed that the PTPRG protein levels were dramatically reduced in the breast cancer tissues compared with the noncancerous tissues (Figure 1A and 1B)

Summary

Introduction

Breast cancer is the most commonly diagnosed invasive cancer worldwide and the second leading cause of cancer death among women. According to the cancer statistics of 2016, breast cancer alone is expected to account for 29% all new cancer diagnoses in women [1]. Protein tyrosine phosphorylation plays a crucial role in regulating biological processes directly relevant to cancer, such as proliferation, differentiation, apoptosis, migration and invasion. This dynamic process is governed by the balanced action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). PTKs catalyze the phosphorylation of tyrosine residues inside cells, whereas PTPs neutralize the effects of PTKs by selectively dephosphorylating their substrates [2]. Alterations in PTPs activity may affect cell growth, neoplastic processes and transformation

Methods

Results

Conclusion