Oral squamous cell carcinoma: microRNA expression profiling and integrative analyses for elucidation of tumourigenesis mechanism
Author(s): Mayakannan Manikandan1 , Arungiri Kuha Deva Magendhra Rao1 , Ganesan Arunkumar1 , Meenakshisundaram Manickavasagam2 , Kottayasamy Seenivasagam Rajkumar3 , Ramamurthy Rajaraman3 and Arasambattu Kannan Munirajan1
Oral cancer broadly encompasses tumours arising in the lips, hard palate, upper and lower alveolar ridges, anterior two-thirds of the tongue, sublingual region, buccal mucosa, retromolar trigone and floor of the mouth . Squamous cell carcinoma is the predominant (~95 %) histological type  and hence the term 'oral cancer' tends to be used interchangeably with oral squamous cell carcinoma (OSCC). In 2012, OSCC accounted for 145,000 deaths worldwide, with less developed regions sharing 77 % of the burden; In India, OSCC is the leading cancer in men and fifth common cancer in women . The widespread practise of smoking or chewing tobacco and alcohol drinking, apart from poor oral hygiene, poor diet and Human Papilloma Virus (HPV) infections may explain this disproportionately higher incidence of OSCC in India [4, 5]. Although the oral cavity is readily accessible for clinical examination, most tumours are not diagnosed until they have advanced or metastasized , thereby limiting the effectiveness of chemotherapy, radiotherapy and surgery. Moreover, the development of second primary tumours hamper the success of multimodal therapeutic procedures leading to poor prognosis and dismal 5-year survival rates [3, 7]. Hence, research directed towards the identification of biomarkers for early diagnosis of OSCC, indicators of good or bad prognosis, and determinants of treatment response/overall survival is undeniably essential .
MicroRNAs (miRNAs) are short (19-to-25 nt) single stranded non-coding RNAs, that bind to complementary sequences present usually in the 3' untranslated region (UTR) of target messenger RNAs and inhibit their translation by the subsequent recruitment of RNA induced silencing complex - RISC [9, 10]. Since > 30 % of the human genes are predicted to be regulated by miRNAs, these tiny RNAs govern all cellular, physiological and developmental processes . MicroRNAs are encoded throughout the genome with a vast majority located in intergenic regions (anywhere between 57 and 69 %), followed by intronic regions (~12 to 17 %), exonic (~5 %), long-noncoding (5 %) and repeat regions (~8 %) . Nevertheless, around 50 % of these genomic regions are frequently prone to alterations in various cancers and are collectively termed as cancer-associated genomic regions (CAGRs) [13, 14]. As a consequence, miRNA deregulation is common in all human cancers including OSCC and miR signatures have been helpful at all levels right from diagnosis to determination of treatment response . Majority of the miRNA expression profiling studies performed in OSCC until now represent either oral cancer cell line models [16, 17] or tissue samples of head and neck carcinoma on the whole [18-23]. Although oral, pharyngeal and laryngeal tumours are grouped together as head and neck squamous cell carcinoma (HNSCC), the process of carcinogenesis is quite different leading to molecular heterogeneity . Moreover, variations in risk factors and associated clinical parameters across different geographical areas of the world adds more complexity to OSCC . Hence, studying OSCC...
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