miRNA and Cancer Diagnostics
By Priyanka Varma
BURLINGAME, Calif.
Apr. 13th, 2022
“miRNA” (micro RNA) are small non-coding regulatory RNA of 17-20 nucleotides in size [1]. Currently, >35,000 miRNA sequences have been identified in >270 organisms. They pair with target mRNA (messenger RNA) to modulate gene expression thereby playing a role in several physiological and pathological processes, like cellular signaling, metabolism, differentiation, and apoptosis. This role leads to its utilization in cancer diagnostics as well as treatment [2].
Breast cancer associated miRNAs can be categorized into oncomiRs (oncogenic miRNAs) and tsmiRs (Tumor suppressor miRNAs). An upregulation of oncomiR and/ or downregulation of tsmiR can lead to development of breast cancer. They work in tandem to help regulate breast cancer development and progression. This complex interplay occurs between cell proliferation, angiogenesis, apoptosis, and cell death etc. [3].
While some miRNAs are expressed differentially in developmental stages, around one third of human miRNA are organized in clusters and expressed unequally. miRNA expression can be measured by several techniques like Northern blot, RNAse protection assay; however, qRT-PCR (quantitative Real Time Polymerase chain reaction) is a test which provides higher sensitive results. Microarray and in-situ hybridization techniques are useful in assessing the miRNome (global expression profile of miRNA). SAGE (Serial Analysis of Gene Expression) is utilized for assessing small RNAs and is benefitted by ultra high throughput sequencing [2]. A detailed and accurate profiling is beneficial in understanding the contribution of miRNA in biological functions and in clinical applications [4]. The miRNOME microarray analysis has elucidated for e.g. that miR-21 is up-regulated while miR-125b and miR-145 are downregulated in breast cancer. Similarly in pancreatic cancer, array analysis identified miR-196a, miR-21, miR-221, miR-22 among others to be upregulated, while miR-217, miR-375, miR-155 were downregulated [2].
Bibliography:
- Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol. 2009;4:199-227. doi: 10.1146/annurev.pathol.4.110807.092222. PMID: 18817506; PMCID: PMC2769253.
- Huang HY, Lin YC, Cui S, Huang Y, Tang Y, Xu J, Bao J, Li Y, Wen J, Zuo H, Wang W, Li J, Ni J, Ruan Y, Li L, Chen Y, Xie Y, Zhu Z, Cai X, Chen X, Yao L, Chen Y, Luo Y, LuXu S, Luo M, Chiu CM, Ma K, Zhu L, Cheng GJ, Bai C, Chiang YC, Wang L, Wei F, Lee TY, Huang HD. miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 2022 Jan 7;50(D1):D222-D230. doi: 10.1093/nar/gkab1079. PMID: 34850920; PMCID: PMC8728135.
- Loh HY, Norman BP, Lai KS, Rahman NMANA, Alitheen NBM, Osman MA. The Regulatory Role of MicroRNAs in Breast Cancer. Int J Mol Sci. 2019 Oct 6;20(19):4940. doi: 10.3390/ijms20194940. PMID: 31590453; PMCID: PMC6801796.
- Gao L, Jiang F. MicroRNA (miRNA) Profiling. Methods Mol Biol. 2016;1381:151-61. doi: 10.1007/978-1-4939-3204-7_8. PMID: 26667459.