miR-193b/365a cluster controls progression of epidermal squamous cell carcinoma

Abstract

Incidence of cutaneous squamous cell carcinomas (cSCCs) constantly increases in the Caucasian population. Developing preferentially on precancerous lesions such as actinic keratoses due to chronic sunlight exposure, cSCCs result from the malignant transformation of keratinocytes. Although a resection of the primary tumor is usually curative, a subset of aggressive cSCCs shows a high risk of recurrence and metastases. The characterization of the molecular dysfunctions involved in cSCC development should help to identify new relevant targets against these aggressive cSCCs. In that context, we have used small RNA sequencing to identify 100 microRNAs (miRNAs) whose expression was altered during chemically induced mouse skin tumorigenesis. The decreased expression of the miR-193b/365a cluster during tumor progression suggests a tumor suppressor role. Ectopic expression of these miRNAs in tumor cells indeed inhibited their proliferation, clonogenic potential and migration, which were stimulated in normal keratinocytes when these miRNAs were blocked with antisense oligonucleotides. A combination of in silico predictions and transcriptome analyses identified several target genes of interest. We validated KRAS and MAX as direct targets of miR-193b and miR-365a. Repression of these targets using siRNAs mimicked the effects of miR-193b and miR-365a, suggesting that these genes might mediate, at least in part, the tumor-suppressive action of these miRNAs.

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma

“…Exosome transfer of miR has been widely studied in the interaction between tumour and its surrounding tissues (Neviani and Fabbri, 2015), thus it is legitimate to speculate that overexpression of miR-193b-3p in cancer could have driven the phenotype we observed. Some observations, however, argue against this theory, as the analysis of an independent cohort of RCC cases and matching controls included in the TCGA data set revealed a downregulation of miR-193b-3p in cancer compared with normal tissues; an observation that fits with several reports suggesting a tumour suppressor role for miR-193b-3p (Gastaldi et al , 2014; Mets et al , 2015). Further evidence supporting this hypothesis is represented by the comparison of RCC-matched normal tissues vs healthy kidney donors.…”

RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action

“…Both miR-193b and miR-365a could acted as a tumor suppressor in the epidermis by directly targeting KRAS oncogene [79]. These results confirmed that clustered miRNAs (i.e.…”

Association of Polymorphisms in three pri-miRNAs that Target Pepsinogen C with the Risk and Prognosis of Gastric Cancer

“…However, in recent years, mir-365 has been shown to inhibit cancer. It is downregulated in lung cancer tissues; inhibits tumor cell line migration222324252627; and promotes apoptosis and regulates bcl-2 expression2324. The results of this study showed that the risk of intestinal-type gastric cancer in the alcohol consumption subgroup was lower with the pri-miR-365b rs121224 C allele, but that the subgroup of patients with Borrmann type III-IV staging had a better prognosis with the G genotype.…”