miR-135 promotes proliferation and stemness of oesophageal squamous cell carcinoma by targeting RERG.

MicroRNA (miRNA) plays an important role in tumourigenesis and cancer development by regulating oncogenes or tumour suppressor that are implicated in cell cycle, cell mobility and even cell senescence. Due to the resistance to enzymes that could degrade nucleotides, miRNAs have been considered proper for diagnosis and prognosis evaluation of cancer. The present study was designed to investigate miRNA associated with ESCC and identified effective miRNAs, which could serve as biomarker or targets. We first performed miRNA profiling to identify a subset of dysregulated miRNAs in ESCC. miR-135, miR-451 and miR-186 were the most differentially expressed miRNAs. Subsequent RT-PCR validated that miR-135 was upregulated in ESCC cell lines TE2 and TE9, implying the promise as a prognostic and diagnostic marker. The Cox regression analysis suggests the correlation of miR-135 expression and tumour stages. Survival analysis demonstrated metastatic samples largely have higher miR-135 expression. Downregulation of miR-135 suppressed proliferation and invasion of TE2 and TE9 cell lines. Subsequent target prediction combined with functional enrichment analysis identified "Small GTPase superfamily" that are possibly targeted by miR-135, which offers candidates for further investigation. Finally, RERG was identified as a target of miR-135. Downregulation of RERG could inhibit the cell proliferation and sphere formation ability of TE2 and TE9. Taken together, miR-135 was proved to promote tumour development of ESCC, which promises the prospect of using miR-135 as a biomarker indicator in diagnosis and prognosis.