Alexander Hsu

Introduction. Hepatocellular carcinoma (HCC) is the most common form of liver cancer in adults, especially in Asian countries, where it is the third most common cause of cancer-related deaths. Most commonly, HCC arises as a result of chronic infection by hepatitis B and C (5). As tumors grow, the amount of oxygen available to each tumor cell is decreased, and so like all tumors, HCC must be able to adapt to hypoxic conditions, changing its expression patterns to drive certain effects such as angiogenesis, metabolic adaptation, survival, and migration. Studies show that tumors accomplish a large majority of these effects by expressing various micro RNAs (miRNAs) in response to hypoxia; specifically, HCC is known to increase expression of miRNA 210, which promotes angiogenesis (4), upregulates glycolytic proteins (already previously established) (2), and increases malignancy (4). Thus by detecting miRNA 210 early or by targeting it in HCC patients, there may be dramatic improvements in prognoses (1,3,4). Methods. MicroRNA 210 stably overexpressed HCC cell lines were established, and inoculated into nude mice, subsequently staining for CD34, which would be increased in vascularization (4). Yang Y. et al. also performed western blots to assess the change in concentration of FGFRL1 in the presence of miRNA 210. Using tumors obtained surgically from HCC patients, they tested for the correlation between tumor progression and miRNA 210 levels (3, 4). Staining with Annexin V/propidium iodide, Costales et al. observed whether the small molecule Targapremier-210 can trigger apoptosis in hypoxic cells (otherwise kept alive by miRNA 210) (1). After using anti-sense miRNA to target miRNA 210 in HCC cells, Yang W. et al. then use the MTT assay to observe cell viability after radiation (3). Results. MicroRNA 210 directly contributes to hypoxic tumor growth, assisting in angiogenesis and malignancy. Suppression of the miRNA not only results in the normal apoptosis of HCC cells, but also in greater sensitivity to radiation. Lastly increased levels of miRNA 210 can serve as a useful marker for HCC for prompt treatment of the disease. Conclusions. Studies indicate that certain micro RNAs are upregulated in different cancers, facilitating the malignant growth of the tumor. In hepatocellular carcinoma, miRNA 210 can not only be targeted as an important mediator of the disease, but also be used as a diagnostic tool for early treatment.

1.  Costales MG, Haga CL, Velagapudi SP, Childs-Disney JL, Phinney DG, Disney MD.  Small Molecule Inhibition of microRNA-210 Reprograms an Oncogenic Hypoxic Circuit. J Am Chem Soc. 2017 Mar 8;139(9):3446-3455.
2. Dang K, Myers KA. The role of hypoxia-induced miR-210 in cancer progression. Int J Mol Sci. 2015 Mar 19;16(3):6353-72. doi: 10.3390/ijms16036353. Review. PubMed PMID: 25809609; PubMed Central PMCID: PMC4394536.
3. Yang W, Sun T, Cao J, Liu F, Tian Y, Zhu W. Downregulation of miR-210 expression inhibits proliferation, induces apoptosis and enhances radiosensitivity in hypoxic human hepatoma cells in vitro. Exp Cell Res. 2012 May 1;318(8):944-54.
4. Yang Y, Zhang J, Xia T, Li G, Tian T, Wang M, Wang R, Zhao L, Yang Y, Lan K, Zhou W. MicroRNA-210 promotes cancer angiogenesis by targeting fibroblast growth factor receptor-like 1 in hepatocellular carcinoma. Oncol Rep. 2016 Nov;36(5):2553-2562.
5. Zhu RX, Seto W-K, Lai C-L, Yuen M-F. Epidemiology of Hepatocellular Carcinoma in the Asia-Pacific Region. Gut and Liver. 2016;10(3):332-339.