MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer

Abstract

BackgroundMicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary.Methodology/Principal FindingsTo explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model.Conclusions/SignificanceOur study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer.

Association of miR-193b Down-regulation and miR-196a up-Regulation with Clinicopathological Features and Prognosis in Gastric Cancer

“…It has been reported that over-expression of miR-196a is associated with apoptosis, invasion, and proliferation in pancreatic cancer (Liu et al, 2013). Also, miR-196a is a putative diagnostic biomarker and therapeutic target for laryngeal cancer (Saito et al, 2013).…”

“…miR-196a is a known onco-miRNA that plays an important role in tumorigenesis and tumor progression (Peng et al, 2010;Sun et al, 2012). Emerging evidence suggests the aberrant over-expression of miR-196a is a frequent event in various cancers, including head and neck squamous cell carcinomas (Severino et al, 2013), laryngeal cancer (Saito et al, 2013), pancreatic cancer (Liu et al, 2013), and gastric cancer (Tsai et al, 2012). It has been reported that over-expression of miR-196a is associated with apoptosis, invasion, and proliferation in pancreatic cancer (Liu et al, 2013).…”

Serum microRNA profiling and bioinformatics analysis of patients with type 2 diabetes mellitus in a Chinese population

“…miR-455-5p can promote melanoma growth and metastasis through inhibition of the tumor suppressor gene, cytoplasmic polyadenylation element binding protein 1 (62). In additiob, miR-455-5p was identified as a molecular signature associated with anaplastic large cell lymphoma (63), basal cell carcinoma (64), endometrial serous adenocarcinomas (65) and laryngeal cancer (66). miR-409-3p suppresses the invasion and metastasis of colorectal (67) and bladder cancer (68), but promotes the tumorigenesis of human prostate cancer (69) and gastric cancer (70).…”

A large scale expression study associates uc.283-plus lncRNA with pluripotent stem cells and human glioma

“…Interestingly, hsamiR-1909-3p was discovered in human ESCs by deep sequencing of small RNA libraries [39] and targeted genes, such as DICER1, SOX2 and NOTCH1 [40]. Hsa-miR-455-5p and hsa-miR-640 were deregulated in several cancers but were not the most abundant isoforms and they have not been well characterized yet [41,42]. Very recently, Liz et al [10] showed that the long ncRNA uc.283-minus controlled pri-miRNA processing.…”