Overexpression of miR‑106a enhances oxaliplatin sensitivity of colorectal cancer through regulation of FOXQ1

Abstract

Chemotherapy resistance poses a major challenge for the clinical treatment of colorectal cancer, therefore, the aim of the present study was to examine its underlying mechanisms. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to determine the microRNA (miRNA)/mRNA and protein expression levels, respectively. A dual luciferase assay was conducted for verification of the interaction between miR-106a and 3′untranslated region (UTR) of Forkhead box Q1 (FOXQ1). Cell viability was assessed using an MTT assay. In the present study, it was demonstrated that miR-106a is involved in regulating oxaliplatin sensitivity of colorectal cancer. Transfection of miR-106a mimics slightly inhibited colorectal cancer cell growth and sensitized colorectal cancer cells to oxaliplatin exposure. In addition, miR-106a overexpression induced a decrease of FOXQ1 at mRNA and protein levels in colorectal cancer cells. The enhanced expression of miR-106a also increased the expression of Wnt target genes, including vascular endothelial growth factor-A and matrix metallopeptidase 2, which were reported to be regulated by FOXQ1. It was predicted and validated that miR-106a could repress FOXQ1 expression via direct binding to 3′UTR. Elevation of miR-106a and a decrease of FOXQ1 expression levels were detected in tumor tissues from patients with oxaliplatin-sensitive colorectal cancer, compared with patients with oxaliplatin-resistant colorectal cancer. Furthermore, there was a significant association between miR-106a and FOXQ1 mRNA levels. In conclusion, the present study demonstrated that miR-106a increased oxaliplatin sensitivity of colorectal cancer cells through direct repression of FOXQ1 expression.

The role of non-coding RNAs in chemotherapy for gastrointestinal cancers

“… 59 It was shown that miR-106a is involved in the regulation of CRC oxaliplatin sensitivity. 60 miR-106a transfection mildly suppressed the growth of CRC cells and rendered them more sensitive to oxaliplatin. Furthermore, miR-106a overexpression decreased the FOXQ1 level in CRC cells at both mRNA and protein levels.…”

“…They concluded that miR-106a increased CRC sensitivity to oxaliplatin through direct suppression of FOXQ1 expression. 60 miR-744 was upregulated in head and neck tumors compared to normal tissues. 61 High plasma levels of miR-744 correlated with chemoresistance and poor prognosis in patients with PC undergoing gemcitabine-based chemotherapy.…”

“…They concluded that miR-106a increased CRC sensitivity to oxaliplatin through direct suppression of FOXQ1 expression. 60 …”

The Role of microRNAs in Regulating Cancer Cell Response to Oxaliplatin-Containing Regimens

“…In addition, miR-106a can suppress the transcription of VEGFA and MMP-2, which are target genes for FOXQ1. 54 MiR-135b functions as a tumor promoter in colorectal cancer. The miR-135b expression is remarkably elevated in colorectal cancer cell lines.…”

MicroRNAs regulating SOX2 in cancer progression and therapy response

“…The miRNA-106a function in chemotherapy has not been completely understood. Although studies demonstrate that miRNA-106a has low expression in chemo-resistant-tumour cells and elevating its expression is correlated with chemosensitivity (Refs 174, 175), a recent study demonstrated miRNA-106a function in providing drug resistance via JAK2/STAT3 axis induction (Ref. 176).…”