RASSF10 gene’s gastric cancer inhibiting mechanisms revealed!

Vaishnavi Kardale, Bioinformatics Centre, Savitribai Phule Pune University

To grow, cells have to divide. A single cell divides into two, and then four, and so on. Finally, we turn into a body with trillions of cells. Each cell undergoes differentiation to get its specialized function. From this, it might be quite clear how essential cell division is to be alive. Cell division’s primary goal is to replicate your genetic material and this it does at a very high speed and with high accuracy.

However, sometimes it makes an error. This error is what we call a mutation. A mutation may not necessarily be bad. It is these errors that lead to variations. If these variations get selected by natural selection they may be passed on from one generation to another. It is these errors that have made us different from our ancestors. But sometimes the error can be bad. Usually, these errors are recognized by our body’s cellular mechanism but if it escapes it may divide and pass on the genetic material along with the errors. Such cells divide uncontrollably. Such cells are cancerous.

The RASSF10 gene:

The RASSF10 (Ras Association domain Family) protein is involved in keeping in check cancer cells. It was found that RASSF10 is downregulated by an epigenetic mutation in cancer cells. The promoter region of the RASSF10 gene gets hypermethylated leading to uncontrolled cell proliferation. This shows that RASSF10 has a very important role in keeping in check cancer cell division. However, its exact mechanism was not known. For the first time, researchers at IIT Madras have revealed the role of RASSF10 in inducing a mitotic arrest by inhibiting Cdk1/cyclin-B kinase complex formation. Nucleophosmin(NPM) was found to be a novel functional target for RASSF10.

Molecular mechanism of the RASSF10 gene:

The cell cycle is a highly regulated process. Its progress is kept in check at various checkpoints in different phases of the cell cycle. The cyclin/Cdk protein and NPM are involved in the regulation of the cell cycle. The expression of RASSF10 and NPM proteins positively correlate with the chances of gastric cancer patient’s survival. This suggests that RASSF10 and NPM may act as potential drug targets to identify the therapeutics for gastric cancer. RASSF10 aids in maintaining the stable level of cyclin-B by inhibiting the cyclin Cdk complex formation. Maintenance of a stable level of Cyclin-B is critical to induce mitotic arrest or stop the cell from dividing. GADD45a is another important protein whose expression is induced under stress. It is dependent on RASSF10 and NPM for its nuclear localization and functioning under genotoxic stress. The study suggests that RASSF10 is an important downstream target and it may be used as a new biomarker for diagnosis and a novel target for the therapy of gastric cancer.

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Reference:

1. Lakshmi Ch, N.P, Sivagnanam, A., Raja, S., & Mahalingam, S. (2021). Molecular basis for RASSF10/NPM/RNF2 feedback cascade-mediated regulation of gastric cancer cell proliferation, Journal of Biological Chemistry https://doi.org/10.1016/j.jbc.2021.100935.

About author:

Vaishnavi Kardale is a master’s student at the Bioinformatics Centre, Savitribai Phule University. She is interested in studying and exploring protein folding mechanisms and wants to study them deeper in the future.

Some of her publications at BioXone are:

1. https://bioxone.in/news/worldnews/the-effect-of-stroke-on-muscle-sarcomere/
2. https://bioxone.in/news/worldnews/comeback-of-tuberculosis-but-its-drug-resistant-now/
3. https://bioxone.in/news/worldnews/a-drug-to-reduce-covid-infection-by-99/
4. https://bioxone.in/news/worldnews/artificial-intelligence-ai-for-efficient-covid-testing/

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