Emerging role of tumor suppressing microRNAs as therapeutics in managing non-small cell lung cancer

Lung cancer (LC) is the 2nd most prevalent cause of deaths after breast cancer across the globe. As per the report of GLOBOCAN published in 2020, about 2.2 million people were diagnosed with LC and among them 2 million people died [58]. LC is mainly associated with smoking, exposure to passive smoking, radiation, exposure to radon gas, exposure to asbestos or other carcinogenic agents [34]. There are two types of LC. These are small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). SCLC accounts for 10–15% of total cases of LC and it undergoes metastasis very fast. SCLC is most common among heavy smokers. NSCLC accounts for about 85% of all LC cases [51]. Despite the level and focus of research to date in managing NSCLC as well as the advancement in LC targeted therapies, the five years survival rate is only only 16% of the total cases [46]. NSCLC affects smokers and people who do not smoke. It mainly arises in bronchi and peripheral lung tissues. Metastasis is a major cause of death in patients with malignant tumors that accounts for about 90% of cancer-associated deaths [6]. Various types of LC are shown in Fig. 1.

NSCLC is classified into three categories including adenocarcinoma, squamous cell carcinoma and large cell carcinoma [53]. Adenocarcinoma is the most common type of LC, about 40% of NSCLC and belong to adenocarcinoma [35]. Adenocarcinomas occur in epithelial cells that form the outside surface of the lungs. The internal surface of lungs is made up of flat cells that are popularly known as squamous cells. The cancer that originates in squamous cell carcinoma. About 25–30% of all NSCLC cases belong to squamous cell carcinoma. The least common type of NSCLC is large cell carcinoma. It accounts for about 10% of NSCLC [31].

In the advancement of technology and to provide a therapeutic effect against LC a number of miRNAs have been identified. MicroRNA (miRNA) expression is one of the distinctive epigenetic biomarkers that has potential for use as a potential effective prognostic marker against various cancer including LC [1], [36], [62]. Recent research has highlighted that miRNA functions as tumor suppressor in LC. It has been reported to change the expression of the target mRNA expression to control the cancer biology. miRNA is small 20–22 nucleotide single stranded non-coding RNA molecules. It was discovered in 1993 [66]. Later, in 2004, Takamizawa et al. described the link between miRNA expression and LC [59]. Only eukaryotes, including humans, contain miRNA, which was first identified in Caenorhabditis elegans [27], [48], [66]. miRNA makes up about 1–5% of the human genome and controls at least 30% of protein-coding genes[30].

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