Research Projects

Head and neck cancer (HNC), the 7th most common cancer globally, poses a significant health concern in India. Despite advancements in treatment, the overall survival rate remains around 50%, with even lower rates observed in cases of metastasis. This emphasizes the importance of mechanistic understanding of HNC to improved diagnostic and therapeutic approaches for its successful management. The field of cancer research has been transformed by high-throughput sequencing, which underscore the crucial role of RNA biomarkers in cancer diagnosis and treatment. Among the various types of non-coding RNAs, long non-coding RNAs (lncRNAs) —over 200 nucleotides in length and lack the ability to encode proteins — have gained attention as key regulators of cellular processes with significant implications for numerous diseases, including cancer. Although many lncRNAs have been linked to various cancer types, their specific roles in HNC remain largely unexplored. In our preliminary study (unpublished), we identified LINC00152 and EMSLR as significantly up-regulated lncRNAs in HNC samples (n=32), as evident by RNA sequencing analysis followed by validation by RT-PCR. Both LINC00152 and EMSLR are also markedly upregulated in the TCGA HNC dataset (normal=44, tumor=519). Their high expression levels are associated with cancer stages and poorer patient survival outcomes in the TCGA dataset. However, the molecular function of LINC00152 and EMSLR, as well as their potential in diagnosis and therapy, remains largely unexamined in HNC, particularly in the context of Indian patients. This proposal aims to evaluate the role of LINC00152 and EMSLR in HNC and their potential as diagnostic and therapeutic target. We will investigate the diagnostic relevance of LINC00152 and EMSLR in a larger cohort of Indian patient samples (n=100), analyzing their association with various clinical factors (stage, grade, metastasis, age, gender, tobacco and alcohol use, and HPV status). Of these two lncRNAs, the one with the higher fold change and better correlation will be selected as a candidate for further functional and therapeutic evaluation. We will manipulate candidate lncRNA’s expression in HNC cells through gene depletion or overexpression, examining effects on proliferation, apoptosis, migration, and invasion. Potential targets of the lncRNA will be predicted by bioinformatics analysis and validated by RT-PCR and western blotting. To assess its therapeutic role, we will examine the lncRNA inhibition using siRNA in HNC xenograft or syngeneic mouse models, both alone and in combination with the chemotherapy drugs, cisplatin or erlotinib. This study would significantly impact biomarker development for HNC in Indian patients and clarify the role of lncRNAs in HNC, thus offering a new therapeutic approach either as a standalone or adjunctive to conventional therapies. All experiments are proposed to be completed within three years, leveraging my expertise for successful execution.