miRNAs – what are they?
Ribonucleic acid is also known as RNA. It is a cell building block that is in all living cells and has structural similarities to DNAThe molecule that contains the genetic information that makes you the person you are.. Three different types of RNA exist in cells:
- Messenger RNA (mRNA),
- Ribosomal RNA (rRNA)
- Transfer RNA (tRNA).
In this blog we will look at mRNA and MiRNAs (micro-RNAs), a shorter version of mRNA. They are in all human cells and are involved in different cell processes. This paper reviewed the evidence that MiRNAs are involved in osteosarcoma (OS) cell growth. It also looks at how they could be used to help in OS treatment.
What do miRNAs have to do with osteosarcoma?
This blog looks at two areas where miRNAs could be beneficial. miRNAs are crucial to OS tumour growth and tumour suppression (both processes stop the tumour growing and the cancer progressing). As well as helping with diagnosis of osteosarcoma, miRNAs are involved in different cell processes. This means that treatments involving miRNAs could target multiple parts of cancer cells and be more effective than existing treatments.
miRNAs could also be used as biomarkers for diagnosing OS. A biomarker is a biological marker of a body process which can help measure or diagnose an illness.
What do miRNAs do in cancer cell production?
Some miRNAS help cells through their various stages (cycles). This could lead to potentially enhancing tumour growth in cancer. There are some miRNAs which are involved in OS because they target cell cycle arrest. Cell cycle arrest is when cell growth (replication) is stopped because the cell has detected damage (such as in cancer).
MiRNAs have been found to influence how OS cells develop and function. This affects the OS cells’ potential to grow and replicate.
Low levels of one miRNA, called miR-449c, corresponds to increased tumour size and advanced tumour stages seen in OS. This means that miR-449c could potentially be used for a targeted therapeutic intervention for OS. Another miRNA, miR-659-3p, is involved in tumour size and progression. In laboratory tests, restoring this miRNA to its usual process significantly affected tumour growth and progression in OS.
Targeting these miRNAs to develop new and more precise OS therapies which inhibit tumour growth and metastasis (spreading) could lead to improved patient outcomes and survival. More research needs to be done into this to develop such therapies.
miRNAs as biomarkers for osteosarcoma
There are several miRNAs which are associated with clinical features of OS. These miRNAs could help diagnose OS by being used as diagnostic biomarkers.
miR-375 is one of these biomarkers of OS. It has significantly lower serum levels in OS patients compared to patients who do not have OS. This miRNA has been linked to advanced stage OS, a larger tumour size and a poor response to preoperative OS treatment.
miRNAs and grade progression in osteosarcoma
OS, and all cancers, are graded. Grading means how severe the cancer is and how far it is spreading in the body. TumourA mass of cells that are growing where they shouldn’t be. Tumours can be benign or malignant. Benign tumours do not spread to other parts of the body whereas malignant tumours are cancerous and have the potential to spread. grade refers to how abnormal (vs healthy) cancer cells appear under a microscope. GradeHow quickly cancer cells are growing and dividing. one is a low-grade cancer where cells look less abnormal and are growing more slowly. It is usually confined to the bone or nearby tissues. Grades two and three are higher grade have much more abnormal looking cells which grow and spread rapidly.
Most OS cases are high grade which means they can spread easily to other organs, such as the lungs. miRNAs play a role in how a tumour develops and its’ grade by regulating cell growth and metastasis. miRNAs could help develop personalised treatments for OS.
miRNAs and chemotherapy
A major challenge in treating cancer is when the drugs used in chemotherapy are limited in effectiveness. This is due to developing drug resistance. Drug resistance allows cancer cells to spread more rapidly and become more aggressive because the drug used is not working as well as it should.
A common drug used in OS chemotherapy is Cisplatin (CDDP). miRNAs have been shown to play a role in regulating drug resistance to Cisplatin in other types of cancers. Using miRNAs to reduce drug resistance in chemotherapy for OS is an opportunity which needs more research.
miRNAs could also help assess chemotherapy effectiveness. Monitoring levels of miR-34a before and after chemotherapy showed low levels of miR-34a returned to a normal level after chemotherapy treatment. This means monitoring this mRNA level can help assess how well chemotherapy has worked. This method has been used in other cancer types so could be rapidly applied to OS.
miRNAs as future treatment for osteosarcoma?
Traditional drugs used in cancer treatment often struggle to be effective because the tumour site is complex. miRNAs can easily access tumour sites because of their very small size. They are also able to influence the cells they are next to (e.g. cancer cells). This means they are more ‘dynamic’ in their activity than usual treatment approaches.
Using mRNI as a therapeutic approach to affect cancer cells and stop them spreading is a new avenue for cancer research. They could be less invasive than traditional treatments such as chemotherapy and surgery. Research into this is in its early stages but is promising.
Though research is in its’ early stages, miRNAs show potential to be affecting in both diagnosing and treating OS. Understanding more about how mRNAs work in targeting cancer cells and improving their effectiveness in treating cancer could lead to treatments being developed for OS. The research is in early stage, but miRNAs have been used effectively in other types of cancer. As OS has poor outcomes, it is important to focus on new treatment methods to improve outcome and survival of these patients.
References:
Boyd, S. Everything you wanted to know about small RNA but were afraid to ask. Lab Invest 88, 569–578 (2008). https://doi.org/10.1038/labinvest.2008.32
Dey M, Skipar P, Bartnik E, Piątkowski J, Sulejczak D, Czarnecka AM. MicroRNA signatures in osteosarcoma: diagnostic insights and therapeutic prospects. Mol Cell Biochem. 2024 Oct 17. doi: 10.1007/s11010-024-05135-5. Epub ahead of print. PMID: 39419925.
Ribonucleic acid (RNA) [Internet]. [cited 2024 Oct 22]. Available from: https://www.genome.gov/genetics-glossary/RNA-Ribonucleic-Acid