Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma

Abstract

MicroRNAs (miRs) are non-coding RNA molecules involved in cancer initiation and progression. Deregulated miR expression has been implicated in cancer; however, there are no studies implicating an miR signature associated with progression in oral squamous cell carcinoma (OSCC). Although OSCC may develop from oral leukoplakia, clinical and histological assessments have limited prognostic value in predicting which leukoplakic lesions will progress. Our aim was to quantify miR expression changes in leukoplakia and same-site OSCC and to identify an miR signature associated with progression. We examined miR expression changes in 43 sequential progressive samples from 12 patients and four non-progressive leukoplakias from four different patients, using TaqMan Low Density Arrays. The findings were validated using quantitative RT-PCR in an independent cohort of 52 progressive dysplasias and OSCCs, and five non-progressive dysplasias. Global miR expression profiles distinguished progressive leukoplakia/OSCC from non-progressive leukoplakias/normal tissues. One hundred and nine miRs were highly expressed exclusively in progressive leukoplakia and invasive OSCC. miR-21, miR-181b and miR-345 expressions were consistently increased and associated with increases in lesion severity during progression. Over-expression of miR-21, miR-181b and miR-345 may play an important role in malignant transformation. Our study provides the first evidence of an miR signature potentially useful for identifying leukoplakias at risk of malignant transformation.

miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review)

“…Those results suggested that the function of miR-181b may be unique, depending on the type of tumor and cellular context (29)(30)(31). It was previously demonstrated that miR-181b is a critical link between inflammation miR-181b as a key regulator of the oncogenic process and its clinical implications in cancer (Review) and malignant transformation (32). STAT3, a transcription factor activated by IL-6 (33-35), directly activates miR-21 and -181b-1 (36).…”

Apoptosis as a Therapeutic Target in Cancer and Cancer Stem Cells: Novel Strategies and Futures Perspectives

“…In fact, antisense inhibition of miR-21 leads to the induction of programmed cell death in neuroepithelial cells, through activation of caspases [159]. This apoptosis induction was also confirmed in breast cancer, colon cancer, pancreas cancer, lung cancer, liver cancer, prostate cancer, stomach cancer and oral squamous cell carcinoma (OSCC) [31,160,161,162,163]. So far, multiple targets of miR-21 have been identified and mapped to anti-apoptotic signalling pathways which suggest a promising miRNA treatment for cancer [31,164].…”

Immunological and classical subtypes of oral premalignant lesions

“…It was found to be upregulated in cancer versus normal mucosa, while its expression changes in hyperplasia, dysplasia and cancer was not consistent across all patients, suggesting that its dysregulation could be different depending on the molecular subtype of OPL. 39 In other contexts, miR142-5p has been reported to play a role into macrophages differentiation 40 and to be down-regulated in glioblastoma-infiltrating macrophages. 41 Overall, the interaction between the immune system and neoplasia reflects a fundamental principle, applicable to all organ/cell types.…”