Volume 180, December 2022, 103850Abstract

Oral or mouth cancer is the 16th most common form of cancer among the world’s topmost malignancies. Healthy lifestyle and control of known risk factors can reduce its incidences further. Patients succumb to oral cancer when diagnosed late and lack timely access to tertiary care. Molecular biomarkers might help in early detection of oral cancer. Recently, researchers have identified numerous microRNAs which play a crucial role in promoting and suppressing oral cancers. miRNAs are short non-coding RNA molecules (18–22 nucleotides) that play a pivotal role in regulating gene expression. Understanding the miRNA interplays in oral cancers could augment the development of potential diagnostic, prognostic, and therapeutic tools. Liquid biopsy- a non-invasive approach that has been used lately, allows the determination of miRNAs in biological fluids that play essential roles in tumor suppression and cancer promotion. Herein, we summarize an update on the role of miRNAs in the diagnosis and treatment of oral cancer.

Section snippetsBackground

Oral malignancies that include lip and mouth cancers are represented among the top global malignancies. According to GLOBOCAN 2020, more than 377,000 new cases and 177,000 annual deaths worldwide are reported due to oral cancers (World Health Organization, 2020). According to WHO, South and South-East Asian countries, including India, Bangladesh, Sri Lanka, and Pakistan, contribute around 40 % of global oral cancer cases. India currently represents the second-highest number of oral cancer

Liquid biopsy in oral cancer diagnosis

A liquid biopsy uses a patient’s bodily fluids like blood/serum/plasma, saliva, urine, CSF (Cerebrospinal fluid), etc., to detect CTC elements (Circulating Tumor Cells), ctDNA (circulating tumor DNA), and miRNA rich exosomes (Fig. 1; Liquid Biopsy and its applications) (Junqueira-Neto et al., 2019). Liquid biopsy for detecting oral cancer could offer a potential diagnostic method.

Molecular profiling through liquid biopsy could diagnose the cancer stage with high precision due to a

miRNA biogenesis

miRNAs are short non-coding RNA molecules that play a crucial role in regulating gene expression. Among the so far discovered non-coding RNAs, miRNAs are explored the most (Hanna et al., 2019) in modern biological researches owing to their gene expression regulation properties. miRNA is mainly transcribed by RNA Pol II and, occasionally, by RNA Pol III (Riffo-Campos et al., 2016). RNA Pol I/III produces a primary RNA (pri-miRNA) inside the nucleus, which is then processed into precursor miRNA

Conclusion

Despite tremendous advancements in the research field, we are yet to untangle the complexity of Cancers. Oral cancer could be effectively managed only if detected at an early stage. Tissue biopsy is still being used as the gold standard for diagnosing oral cancer; however, recently, Liquid biopsy has been implemented in cancer studies considering its advantage of being a non-invasive and relatively economical approach. miRNAs are the body’s internal and crucial gene expression regulators whose

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Funding

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Author Contributions

Ghulam Mehdi Dar: Conceptualized, designed, and drafted the manuscript, Shreya Agarwal, Renu Verma, Real Sumayya Abdul Sattar Nimisha, Arun Kumar, Apurva, and Abhay Kumar Sharma: Helped in literature survey and manuscript preparation, Ejaj Ahmad, Asgar Ali, and Bhawna Mahajan: Critically reviewed the manuscript, Sundeep Singh Saluja and Ravi Meher: Guided, reviewed and gave final consent for publication.

Competing interests

The authors declare that they have no competing/conflicting interests.

Acknowledgments

The authors acknowledge the facilities provided by Govind Ballabh Pant Postgraduate Institute of Medical Education and Research (GIPMER), New Delhi, India. Authors are grateful to the Department of Biotechnology (DBT) for the financial support provided under the head of “Establishment of Central Molecular Lab in GIPMER to study the diagnosis for precision medicine in order to understand the disease process and utilize it as Clinical Research Facility” with grant no. BT/INF/22/SP33063/2019. We

Ghulam Mehdi Dar, M.Sc., is working as Research Assistant at Central Molecular Laboratory, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER. Currently, he is handling the project that aims to explore the cell free DNA of AMI patients for potential biomarkers using bioinformatic analysis. Furthermore, he is interested in cancer biology especially oral cancers, breast cancers and gliomas. In addition to that his research interests include cardiovascular

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Ghulam Mehdi Dar, M.Sc., is working as Research Assistant at Central Molecular Laboratory, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER. Currently, he is handling the project that aims to explore the cell free DNA of AMI patients for potential biomarkers using bioinformatic analysis. Furthermore, he is interested in cancer biology especially oral cancers, breast cancers and gliomas. In addition to that his research interests include cardiovascular biology, bioinformatics, and cellular/molecular biology.

Shreya Agarwal, M.Sc., is a Technical Assistant & about to get enrolled soon for Ph. D. Her work is based on detection & diagnosis of Oral Cancer using NGS technique. Her Area of interest is based on Molecular analysis in relation with clinical trials on patients suffering from Oral Cancer Diseases. Furthermore, her research interests include the oral microbiome and has recently started to explore pathways of HPV mediated oral cancers in the Indian population.

Renu Verma received her Ph.D. degree in Biotechnology from Guru Gobind Singh Indraprastha University, New Delhi, in 2019. She was awarded a research fellowship from University Grants Commission, India. Currently, she is a research associate at Central Molecular Laboratory, Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER). Her research interests include cancer biology, cancer biomarkers, and gastro-esophageal cancer.

Real Sumayya Abdul Sattar, Ph.D., is a research associate at Govind Ballabh Pant Institute of Post Graduate Medical Education and Research (GIPMER). Her main research interest includes molecular analysis of cancer associated genes to explore their potentiality as molecular biomarkers for early screening, diagnosis, and prognosis of cancer (GI cancers and breast cancer).

Nimisha is a Ph.D. student enrolled at Central Molecular Laboratory, GIPMER in collaboration with Jamia Millia Islamia University, Delhi. Her research work is mainly focussed on gall bladder cancer.

Apurva is a Senior Research Fellow. She enrolled for Ph.D. at Central Molecular Laboratory, GIPMER in collaboration with Amity University, Noida. Her area of interests includes molecular analysis of GI cancer and periampullary carcinoma.

Arun Kumar is a technical assistant and will soon get enrolled for Ph.D. His work is largely focused on the analysis of gut microbiome and their metabolites by high throughput sequencing technology in colorectal cancer. His area of interests includes molecular and computational analysis of gastrointestinal cancers using bioinformatics pipelines.

Abhay Kumar Sharma is working as a Senior Research Fellow at GIPMER, New Delhi and got enrolled in PhD program at Patna University, Patna. His research interest has been focused on molecular oncology and cell death mechanism in cancer. He has a keen interest in understanding the mechanism of genetic as well as epigenetics modification and alteration in junk DNA sequence of oncogene and tumor suppressor gene with the goal of improving clinical outcomes for cancer patients.

Ejaj Ahmad is working as a Scientist C in Central Molecular Laboratory, GIPMER, and has nearly 10 years post Ph.D. research experience in the area of the nose to brain delivery of nanomedicine, development of smart nanomedicine to overcome multiple oral barriers to increase the bioavailability of insulin, and cancer biology. Dr. Ahmad obtained a Ph.D. degree in Biotechnology in 2011 from Aligarh Muslim University, Aligarh, India. He worked as an Assistant Professor from 2011 to 2014 and was involved in subunit vaccine development against infectious diseases. He subsequently moved to Shanghai and worked as a Postdoc Fellow in the Department of Pharmaceutics, School of Pharmacy, Fudan University between 2015 and 2017 and Research Scientist in the Department of Drug Discovery Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai between 2017 and 2019. Dr. Ahmad has vast research experience which can be assessed by his publication record. He has published nearly 30 research articles of international reputes that include PNAS, ACS Nano, Nanoscale, ACS Applied Material Interface and Applied Material Today, etc. Needless to mention, Dr. Ahmad has also received a highly prestigious research grant from the Shanghai government during 2017–2019.

Asgar Ali is a molecular biologist (Project Manager) in the Department of Biochemistry, AIIMS, Patna. He worked for Ph.D. at Devi Ahilya Vishwavidyalaya, Indore and Jamia Millia Islamia, New Delhi. He has more than 10 years of research experience in the field of molecular oncology and has published his findings in National/International journals. He has also written a book chapter on cancer genetics and directs a SERB-DST-funded project as a National Post-Doctoral Fellow. Dr Ali has been awarded ‘Best Science Research Award’ by Madhya Pradesh Council of Science and Technology, Bhopal, India as well as several international travel awards. He is peer reviewer of various National/International journals and member of Scientific/Societies/other professional bodies.

Bhawna Mahajan is a Professor in the Department of Biochemistry, GB pant hospital (GIPMER). She holds a MD degree in Biochemistry. She has been working on a project entitled “Bioinformatics analysis of methylome status of circulating DNA in Acute Myocardial Infarction and exploration of its biomarker utility”. She is co- investigator of different DBT funded projects and theses of MD, MS and M.ch. students, who are working in different diseases viz Glioma, CAD, GI medicine

Sundeep Singh Saluja is a Gastro-intestinal surgeon and oncologist since 20 years and has obtained his M.S. from UCMS & GTBH, New Delhi and M.Ch. in gastro-intestinal surgery from AIIMS, New Delhi. He had a keen interest in molecular pathogenesis of cancers to decipher underlying mutations that could be used clinically to improve the treatment of cancer patients. He established a well-organized central molecular laboratory to undertake research in cellular, molecular, genomics and proteomic aspects of various cancers, gut microbiome, neurological and metabolic diseases. He has been working to search novel molecular targets, which could be implemented into clinical practice as potential diagnostic/prognostic markers for cancer. The significant findings of his work have been published in reputed international journals, including Cancer Genetics, Oncology, tumor biology and Pharmacological Research. He has been awarded many prestigious fellowships and research grants from various funding agencies viz. DBT, ICMR etc. He is also mentoring research work of Ph.D. students at Govind Ballabh Pant Institute of Postgraduate Medical Education and Research. His current areas of interest are identification of biomarkers for early diagnosis of esophageal cancer and gall bladder cancer using next generation sequencing. His team has been working towards unveiling the clinical as well as molecular aspect in different cancers.

Dr Ravi Meher started his medical career as an undergraduate student of MBBS at Maulana Azad Medical College, one of the premiere medical colleges of India in 1992. In 1998, he joined the ENT department of Maulana Azad Medical College as junior resident. He pursued post-graduation in the field of Otolaryngology – Head and Neck Surgery, was conferred with M.S. (Master of Surgery) Otolaryngology in 2001 by the University of Delhi, and subsequently in the same year of 2001, obtained Indian Board Certification in Otolaryngology – HNS, and was conferred with D.N.B (Diplomate of the National Board). In Jan 2002 he joined as specialist registrar. He has been a member of Teaching Faculty since May 2005, and for the past 14 years employed as a teaching faculty in the ENT department of Maulana Azad Medical College, and currently as Director Professor. He has several academic distinctions, prizes, awards and medals to his credit. He is Fellow of American College of surgeon and is also member of National academy of medical sciences and international working group of Endoscopic ear surgeons. He is recognized PG guide and examiner for various university across country. He has special interest in the field of endoscopic surgery, skull base surgery and head and neck oncology. He has more than 125 publications in national and international journals and has been invited to numerous conference and workshop as faculty.

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