TERT Gene

Introduction

KRAS, HRAS, and NRAS are three genes in the RAS pathway which influence the MAPK/ERK pathway. The KRAS gene directly affects different types of cancer. One specific example is lung cancer. 3 different mutations cause a normal lung cell to turn into lung cancer. KRAS is a gene that controls the protein K-Ras. When this protein is activated, it relays signals causing the cell to proliferate. If this gene is mutated it can cause the cell to reproduce without stopping causing a tumor.

Mechanism

The MAPK/ERK pathway is a signaling system used by cells. It is made up of the RAS family, Tyrosine Kinase Receptor, and many other proteins. KRAS directly affects the proliferation and differentiation of the cell. The KRAS gene affects the protein K-RAS in the pathway. If the miRNA let-7 doesn’t bind to the KRAS gene, then the K-RAS protein will be deformed and too many copies will be produced. The K-RAS gene is formed without a GTP/GDP receptor which causes it to be on all the time. GTP/GDP is a power source similar to ATP used in cell energetics. Guanosine Triphosphate is the high energy molecule which the K-RAS protein uses to turn on. Then it is converted to GDP which goes on to become GTP again.

Discussion & Future direction

There are a few treatments available. One treatment specific about NSCLC & KRAS is LUMAKRAS. It targets the specific K-RAS proteins which are stuck in the on-position, always sending signals to the cell. LUMAKRAS (sotorasib) blocks the signals from being sent. After stopping the signals the tumor wil most likely stop. This treatment is approved by the FDA and is used by NSCLC patients.

_ By: Aarush Gogineni, Stratford Middle School _ (External student, guest post on the request of Mentors)

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661921/

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678952/

3. https://www.frontiersin.org/articles/10.3389/fimmu.2020.589929/full

4. https://link.springer.com/article/10.1007/s40291-018-0336-x

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226422/

6. https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Glioblastoma-Multiforme

7. https://www.mayoclinic.org/diseases-conditions/glioblastoma/cdc-20350148

8. https://academic.oup.com/noa/article/2/1/vdaa025/5763093

9. https://www.sciencedirect.com/science/article/pii/S030438352030358X#undfig1

10. https://www.pnas.org/doi/full/10.1073/pnas.1303607110

11. https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-016-0324-x

12. https://medlineplus.gov/genetics/gene/tert

13. https://modbase.compbio.ucsf.edu/modbase-cgi/model_details.cgi

14. https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=TERT

15. https://www.cbioportal.org/results/oncoprint

16. https://www.ncbi.nlm.nih.gov/gene/7015

17. https://www.uniprot.org/uniprotkb/O14746/entry

18. https://www.nature.com/articles/ncomms3185​​

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of Elio Academy.