microRNA biomarkers in cancer diagnosis and treatment: Applications in lung cancer

 

-By Dr. Akash G Prabhune

 

 
MicroRNAs (miRNAs) are a class of single stranded, small, endogenous ribonucleic acids (RNAs) of 21–25 nucleotides in length found in both animal and plant cells(Wahid et al., 2010).miRNAs play regulatory roleby targeting specific messenger RNAs (mRNAs) for degradation or translation repression(Ambros, 2004). In this article, we will concentrate on miRNAs in animal cells; miRNAs have an important role in regulating the physiological processes in animal cells. Multiple knockout gene studies have been conducted on zebra fish, demonstrated that microRNA miR-1-2 are responsible for cardiac muscle development and excess miR-1 in the developing heart leads to a decreased pool of proliferating ventricular cardiomyocytes(Zhao et al., 2005). Similarly, microRNA-155 (miR-155) has an important role in the mammalian immune system by regulating T cell differentiation(Thai et al., 2007).

Even though miRNAs were known to be important in regulation of physiological process in animal cells, the major breakthrough was achieved when a study demonstrated that the downregulation of miR15 and miR16 was seen in cases of Chronic lymphocytic leukaemia (CLL)(Calin et al., 2002). This lead to extensive research in understanding the relationship of miRNAs and cancer development; a paper published in CA Cancer J Clin 2014 summarizes the

cancer hallmarkrole of miRNAs in all stages of cancer development in Image 1.miRNA let-7 activate RAS oncogene which brings sufficiency in growth signals leading to over growth of cells, miR-17-92 brings about activation of E2F factor which insufficient anti-growth signals further increasing the cell differentiation. MiR-25 prevents cell apoptosis, miRNA-373 and miRNA-372 were identified as capable of allowing proliferation and tumorigenesis of primary human cells. miR-10b was found responsible for metastasis of lung cancer cells(Berindan-Neagoe et al., 2014).

Considering the involvement of miRNAs in every stage of cancer, miRNAs have been extensively studied to be used as biomarkers for early detection and diagnosis of cancers(Del Vescovo et al., 2014). Lung cancer being one of the most common cancer globally with high mortality due to prognosis has been subjected to various trials to determine and validate miRNA biomarkers, which can lead to early detection of lung cancer(Inamura and Ishikawa, 2016). A study conducted using sputum specimens of 40 individuals examined the expression of miRNA-21 which is an overexpressed microRNA in lung cancer was able to differentiate 23 Non-small cell lung cancer (NSLC) specimens form 17 cancer free specimens with 70% sensitivity and 100% specificity(Xie et al., 2010). Another study that used three plasma microRNAs (miR-21miR-210, and miR-486-5p) demonstrated 75% sensitivity and 85% specificity while differentiating malignant solitary pulmonary nodules (n = 32) form benign solitary pulmonary nodules (n = 33)(Shen et al., 2011). The advantage of using miRNAs as biomarkers in early detection being miRNAs are found in abundance in human body, a miRNA can be extracted from serum, blood, plasma, as a non-invasive technique. Furthermore, miRNAs can be obtained from biopsy tissues(Price and Chen, 2014). Animal studies are being conducted to understand the role of miRNAs as biomarker in predicting the recurrence and survival of cases underwent surgery of treatment of lung cancer. miRNA-34amiRNA-214 have been studied in animal models to predict the outcome and resistance to radiotherapy(Florczuk et al., 2017).

Overall miRNAs present as biomarkers with great potential in early detection to predicting the recurrence of cancer due to their wide spread role in regulating the physiological cell functions. Recent advances in sciences made it possible to study and explore large number of miRNAs, more clinical studies are required to establish miRNAs as a valid biomarker in oncology research.

References

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  • Berindan-Neagoe, I., Monroig, P., Pasculli, B., Calin, G.A., 2014. MicroRNAome genome: a treasure for cancer diagnosis and therapy. CA. Cancer J. Clin. 64, 311–336. doi:10.3322/caac.21244
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