The oncogenetic role of microRNA-31 as a potential biomarker in oesophageal squamous cell carcinoma

Abstract

miR-31 (microRNA-31) is frequently altered in numerous cancers. The aim of the present study was to investigate the role of miR-31 in ESCC (oesophageal squamous cell carcinoma). We measured miR-31 in 45 paired ESCC tissues and 523 serum samples using real-time RT (reverse transcription)-PCR. The serum samples were divided into a discovery group (120 ESCCs and 121 normal controls), a validation group (81 ESCCs and 81 controls), and a final group comprising six other common tumours (colorectal, liver, cervical, breast, gastric and lung cancers; total n=120). A Mann-Whitney U test and Wilcoxon matched-pairs test were used for the statistics. miR-31 was up-regulated in 77.8% of the ESCC tissues. Serum miR-31 levels in ESCC patients were significantly higher than in normal controls (P<0.001). It yielded an ROC (receiver operating characteristic) AUC (area under the curve) of 0.902 [95% CI (confidence interval), 0.857-0.936] in the discovery group and a similar result in the validation group [ROC AUC, 0.888 (95% CI, 0.819-0.939)]. Patients with high-levels of serum miR-31 also had a poorer prognosis in relapse-free survival (P=0.001) and tumour-specific survival (P=0.005). In vitro studies showed that miR-31 promoted ESCC colony formation, migration and invasion. Luciferase reporter and Western blot assays confirmed that three tumour suppressor genes, namely EMP1 (epithelial membrane protein 1), KSR2 (kinase suppressor of ras 2) and RGS4 (regulator of G-protein signalling 4), were targeted by miR-31. We conclude that miR-31 plays oncogenetic functions and can serve as a potential diagnostic and prognostic biomarker for ESCC.

MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer

“…miR-31 is reported to have tumor-suppressing functions, and its expression is decreased during tumorigenesis in several types of cancer, including breast, ovarian, prostate, bladder, hepatocellular, and gastric carcinoma and melanoma (9)(10)(11)(12)(13)(14)(15)(16). In contrast, a proproliferative function for miR-31 was reported in colorectal, head and neck squamous cell, small-cell lung, and esophageal squamous cell carcinoma (13,(17)(18)(19)(20). In the lung, miR-31 overexpression was observed in lung cancers from cyclin E transgenic mice and in 2 of 3 human lung adenocarcinomas and all 3 lung squamous cell carcinomas analyzed (21).…”

Investigation of nonspecific cross-reacting antigen 2 as a prognostic biomarker in bone marrow plasma from colorectal cancer patients

“…MiRNA expression patterns have also been shown to be associated with diagnosis and prognosis in several tumor types [149][150][151][152][153][154]. An interesting study showed that miRNA expression levels could accurately identify cancer tissue origin from metastatic tumors based on a miRNA expression library consisting of 48 miRNAs from 22 different cancer types thereby implicating that miRNAs are tissue specific [155].…”

Human miR-31 targets radixin and inhibits migration and invasion of glioma cells

“…EMP1and RGS4 were recently validated as the direct target of miR-31 in oesphageal squamous cell carcinoma (30). However, whether EMP1 and RGS4 are direct targets of miR-31 in glioma cells remains to be studied.…”