Novel Bioinformatic Approaches to Understand Old Mysteries of RNA Biology in Cancer

Work done in the lab of Dr. Prasanna Kumar Santhekadur at the Centre of Excellence in Molecular Biology & Regenerative Medicine, Department of Biochemistry, JSS Medical College, JSSAHER.

About author

Mr. Shreyas H. K. is currently a graduate student at Dr. Prasanna Kumar Santhekadur’s lab at the Center of Excellence in Molecular Biology and Regenerative Medicine at JSS Medical College, JSS Academy of Higher Education and Research, Mysuru. He completed his Masters in Molecular Biology from the University of Mysore (2021). Before joining Dr. Prasanna’s lab, he worked as a Research Fellow at the Manipal School of Life Sciences, MAHE. During his M.Sc., he worked as an intern in various labs at DBT-RGCB, NIMHANS, HBCSE-TIFR, and MAHE. Here, Shreyas is sharing his work “Novel Insights on MEG3/miR-664a-3p/ADH4 axis in Hepatocellular Carcinoma from an In silico Perspective,” which was recently published in Genes, 2022.

Interview

How would you explain your research outcomes to the non-scientific community?

Well, I was listening to a TEDx expert talk by Dr. Pamela Peeka where she goes on to say, “You are What your Grandparents ate.” This might sound bizarre and interesting at the same time. It is true that we now have an exclusive branch of study that deals with processes and mechanisms that cannot be explained by Classical Genetics, something which we call “Epigenetics” (quite literally translates to beyond genetics). Such epigenetic modifications include mechanisms involving RNA molecules like microRNAs, long-noncoding RNAs, etc., that affect the expression of your genes located within your cells. These epigenetic mechanisms are now appreciated to be a driving force in almost all diseases, including cancers.

Our lab focuses on liver health and associated areas, and my work revolves explicitly around understanding the epigenetic factors behind Hepatocellular carcinoma. In our paper “Novel Insights on MEG3/miR-664a-3p/ADH4 axis in Hepatocellular Carcinoma from an In silico Perspective”, we try to understand how one of the long non-coding RNA (lncRNA) named Maternally Expressed Gene 3 (MEG3) interacts with a microRNA-664a (miR-664a-3p) to ultimately affect the expression of a protein called Alcohol Dehydrogenase IV in Hepatocellular carcinoma.

Today’s society is data-based and data-driven. Likewise, even in the field of cancer biology, there is an ample amount of data waiting to be looked at and analyzed. In our paper, we take the help of big data on cancer and go on to discuss RNA-RNA interactions and validation of their expressions with a particular interest in HCC.

How do these findings contribute to your research area?

We have previous reports and in vitro studies that predict the interactions between MEG3, miR-664, and ADH4-mRNA. MEG3 is a well-known lncRNA to be downregulated in HCC. MEG3 is also known to interact with several target genes, including miRNAs, and alter the expression landscape in human cancers. miR-664a-3p is reported to be highly upregulated in HCC. Through our work, we have predicted and constructed interaction models between the three RNAs [lncRNA (MEG3), miRNA (miR-664a-3p), and an mRNA (ADH4)] using a robust bioinformatic pipeline to show the specific nucleotides of interactions and binding energies involved in such interactions and their implications in HCC. This pipeline that we have employed can not only be used to predict other RNA-RNA interactions in HCC but can also be used to predict similar interactions in other malignancies as well.

What was the exciting moment during your research?

Although I have prior experience working as a research fellow in a similar field, I am currently in the beginning years of my Ph.D., and I believe I am naïve in terms of understanding concepts related to cancer biology. I would say that this approach of open-mindedness, fuelled by keen observation of the available data, made me arrive at a conclusion that took the form of a research article. The relevance of the field of epigenetics in our day-day life itself is enormous and the driving force for me to take up research in the field.

“This pipeline that we have employed can not only be used to predict other RNA-RNA interactions in HCC but can also be used to predict similar interactions in other malignancies as well.”

What do you hope to do next?

I am currently in the first year of my Ph.D. at the Centre of Excellence in Molecular Biology & Regenerative Medicine under Dr. Prasanna Kumar Santhekadur at JSS Medical College, Mysuru. The coming days are equally challenging and promising for me as I will be working on characterizing microRNA clusters in HCC, a relatively unexplored area when it comes to HCC epigenetics.

Where do you seek scientific inspiration from?

I seek scientific inspiration and the urge to do science from several directions. Some are self-driven, while some are sought after! All my mentors, including my school teachers, former research guides, and my current advisor, are sources of inspiration who sparked that urge in me to get into research. A special place is always reserved for our M.Sc. coordinator, Prof. N.S. Devaki molded and gave directions to our ideas and aspirations. Additionally, my self-belief of “being in charge of my work” keeps me on track and pushes me forward. Every day is a new day filled with new hopes and opportunities. At this point, all I can say is that I am fortunate that my area of interest and thought process are perfectly aligning with my mentor’s approach and lab atmosphere, creating a conducive environment for me to explore my area of interest.

How do you intend to help Indian science improve?

There is no science without collaboration. Collaboration does not only mean working on projects jointly, but it can also be a discussion in a small yet healthy setup where we can openly pitch in our ideas and share our views. Collaborative individualism is the key that I would like to stress upon and what we all need to work on to uplift the scientific standards of Indian science.

Reference

Karunakara, S. H., Puttahanumantharayappa, L. D., Sannappa Gowda, N. G., Shiragannavar, V. D., & Santhekadur, P. K. (2022). Novel Insights into MEG3/miR664a-3p/ADH4 Axis and Its Possible Role in Hepatocellular Carcinoma from an in Silico Perspective. Genes, 13(12), 2254. https://doi.org/10.3390/genes13122254

Copy Editor

Manveen K Sethi

Instructor of Biochemistry at the Boston University School of Medicine, USA.

Manveen did her Ph.D. at Macquarie University (MQ), Australia, under the primary supervision of Dr. Morten Thaysen-Andersen, an internationally recognized researcher in Glycobiology. During her Ph.D., she forayed into colorectal cancer (CRC) research. After her Ph.D., she was offered a postdoctoral research fellowship at Boston University School of Medicine (BUSM), USA, under Prof. Joseph Zaia, an internationally-acclaimed leader in mass spectrometry (MS) and Glycoscience, where she is currently employed in a research faculty-track position of Instructor. Her research work involves identifying and characterizing biomolecules such as proteins and glycans using mass spectrometry techniques and utilizing this information to understand biomolecular deregulation in human diseases, such as cancer and Alzheimer’s disease (AD). In addition, she also serves as an Instrument Manager for Thermo QExactive HF mass spectrometer at Center for Biomedical Mass Spectrometry, Boston University, President of Boston Glycobiology Discussion Group (BGDG), and as a reviewer for many renowned scientific journals. She has recently been awarded her first fellowship grant as an independent P.I. from BrightFocus Foundation to investigate the role of extracellular matrix components in AD. Her long-term career objective is to establish an analytical glycobiology research group with a focus on unraveling the biomolecular deregulations in neurodegenerative disorders, specifically AD.

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