A quest for miRNA bio-marker: a track back approach from gingivo buccal cancer to two different types of precancers.

Navonil De Sarkar,Bidyut Roy,Ranjan Rashmi Paul,Indranil Mukhopadhyay,Arnab Chakraborty,Sandip Ghose,Jit Kumar Mitra,Roshni Roy,Ratna B Ray

doi:10.1371/journal.pone.0104839

Abstract

Deregulation of miRNA expression may contribute to tumorigenesis and other patho-physiology associated with cancer. Using TLDA, expression of 762 miRNAs was checked in 18 pairs of gingivo buccal cancer-adjacent control tissues. Expression of significantly deregulated miRNAs was further validated in cancer and examined in two types of precancer (leukoplakia and lichen planus) tissues by primer-specific TaqMan assays. Biological implications of these miRNAs were assessed bioinformatically. Expression of hsa-miR-1293, hsa-miR-31, hsa-miR-31* and hsa-miR-7 were significantly up-regulated and those of hsa-miR-206, hsa-miR-204 and hsa-miR-133a were significantly down-regulated in all cancer samples. Expression of only hsa-miR-31 was significantly up-regulated in leukoplakia but none in lichen planus samples. Analysis of expression heterogeneity divided 18 cancer samples into clusters of 13 and 5 samples and revealed that expression of 30 miRNAs (including the above-mentioned 7 miRNAs), was significantly deregulated in the cluster of 13 samples. From database mining and pathway analysis it was observed that these miRNAs can significantly target many of the genes present in different cancer related pathways such as “proteoglycans in cancer”, PI3K-AKT etc. which play important roles in expression of different molecular features of cancer. Expression of hsa-miR-31 was significantly up-regulated in both cancer and leukoplakia tissues and, thus, may be one of the molecular markers of leukoplakia which may progress to gingivo-buccal cancer.

Highlights

Gingivo buccal squamous cell carcinoma (GBSCC) is one of the most prevalent (,60%) cancers in oral cavity, especially among the tobacco users in India
Gene expression studies revealed that many miRNAs are deregulated in different cancer types and functional studies clarified that miRNAs are involved in several molecular and biological processes that drive tumorigenesis [10,11,12]
We studied expression deregulation of 762 miRNAs in GBSCC and checked whether similar kind of expression deregulation could be observed in precancerous leukoplakia and lichen planus tissues from oral cavity

Summary

Introduction

Gingivo buccal squamous cell carcinoma (GBSCC) is one of the most prevalent (,60%) cancers in oral cavity, especially among the tobacco users in India. It has been demonstrated that microRNAs (miRNAs) are involved in human tumorigenesis and could act either as tumorigenic/oncogenic or anti-tumorigenic molecules It is making a new layer in the molecular events in human cancer. In addition to different scales of variability in terms of new mutations in genome or genetic background of the patients (i.e. germ line mutation), variability in expression of different miRNAs is a major aspect for investigation. With this belief, we studied expression deregulation of 762 miRNAs in GBSCC and checked whether similar kind of expression deregulation could be observed in precancerous leukoplakia and lichen planus tissues from oral cavity. Efforts have been made to understand how these miRNAs may be involved in cancer using pathway analysis and information from literatures and databases

Methods

Results

Conclusion