A Quest for miRNA Bio-Marker: A Track Back Approach from Gingivo Buccal Cancer to Two Different Types of Precancers

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.

Expression deregulation of mir31 and CXCL12 in two types of oral precancers and cancer: importance in progression of precancer and cancer

“…Restoration of expression of these miRNAs causes significant inhibition of cell proliferation, migration, invasion and tumorigenesis as well as significant increase in apoptosis161819202122. Only few reports are available regarding expression of miR-1293 in cancer3 but expression was found to be up-regulated in cancer, leukoplakia and lichen planus tissues in this study (Table 2). …”

“…up- or down-regulation) when compared with control tissues collected from either adjacent site of cancer tissue or healthy individuals (Table 1). In case of leukoplakia, expression deregulation of only mir-31 and mir-31* was in same direction when compared with control tissues from either adjacent site3 or different healthy individuals (Table 2). In Lichen planus tissues, expression of none of these miRNAs was deregulated when compared to adjacent controls3 but most of them have deregulated expression when compared to control tissues taken from different healthy individuals (Table 2).…”

“…In case of leukoplakia, expression deregulation of only mir-31 and mir-31* was in same direction when compared with control tissues from either adjacent site3 or different healthy individuals (Table 2). In Lichen planus tissues, expression of none of these miRNAs was deregulated when compared to adjacent controls3 but most of them have deregulated expression when compared to control tissues taken from different healthy individuals (Table 2). In this study, most of the seven miRNAs was found to be up-regulated in LK and LP with respect to normal tissues collected from healthy individuals (Table 2).…”

“…Paired samples: cancer and adjacent control tissue from same patients (published data)3.Unpaired samples: cancer and control tissues from cancer patients and healthy individuals, respectively. * Significant with P value <0.05 after Benjamini-Hochberg multiple testing correction for all miRNAs.↑: upregulation; ↓: downregulation of expression.…”

Genomewide miRNA profiling of oral lichenoid disorders and oral squamous cell carcinoma

“…MicroRNAs seem to play an important role in cancer development and progression, acting as oncogenes or tumor suppressor genes (Kent and Mendell, ). Furthermore, changes in microRNA expression profiles have been reported during malignant transformation from premalignant lesions to squamous cell carcinoma of the head and neck (Cervigne et al , ; Wu et al , ; De Sarkar et al , ).…”