MiRNA-148a Enhances the Treatment Response of Patients with Rectal Cancer to Chemoradiation and Promotes Apoptosis by Directly Targeting c-Met.

Jaw-Yuan Wang,Po-Jung Chen,Ching-Chun Li,Wei-Chih Su,Ching-Wen Huang,Chun-Ming Huang,Yen-Cheng Chen,Ming-Yii Huang,Hsiang-Lin Tsai,Tsung-Kun Chang

doi:10.3390/biomedicines9101371

Abstract

Patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) have an excellent prognosis, but only approximately 30% of patients achieve pCR. Therefore, identifying predictors of pCR is imperative. We employed a microRNA (miRNA) microarray to compare the miRNA profiles of patients with LARC who achieved pCR (pCR group, n = 5) with those who did not (non-pCR group, n = 5). The validation set confirmed that miRNA-148a was overexpressed in the pCR group (n = 11) compared with the non-pCR group (n = 40). Cell proliferation and clonogenic assays revealed that miRNA-148a overexpression radio-sensitized cancer cells and inhibited cellular proliferation, before and after irradiation (p < 0.01). Apoptosis assays demonstrated that miRNA-148a enhanced apoptosis before and after irradiation. Reporter assays revealed that c-Met was the direct target gene of miRNA-148a. An in vivo study indicated that miRNA-148a enhanced the irradiation-induced suppression of xenograft tumor growth (p < 0.01). miRNA-148a may be a biomarker of pCR following NACRT and can promote apoptosis and inhibit proliferation in CRC cells by directly targeting c-Met in vitro and enhancing tumor response to irradiation in vivo.

Highlights

Introduction conditions of the Creative CommonsColorectal cancer (CRC) is the leading cause of cancer mortality worldwide, and approximately 30% of CRC cases are rectal cancer [1]
The results indicate the synergistic effects of miRNA148a overexpression with irradiation on apoptosis in CRC cells
To investigate whether miRNA-148a functioned consistently in cells bearing distinct gene mutations, we examined the biological functions of miRNA-148a by using two CRC

Summary

Introduction

Colorectal cancer (CRC) is the leading cause of cancer mortality worldwide, and approximately 30% of CRC cases are rectal cancer [1]. Neoadjuvant chemoradiotherapy (NACRT) is the standard treatment for patients with locally advanced rectal cancer. The response to NACRT is heterogeneous, ranging from chemoradioresistance to pathological complete response (pCR). 15–30% of patients with LARC achieve pCR following NACRT [2,4,5]. Patients with a pCR experience excellent oncological outcomes and may not require adjuvant chemotherapy [6,7]. Reliable predictive biomarkers of pCR to NACRT must be identified for personalized therapy

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Conclusion