Lung carcinoma is one of the leading causes of global cancer mortality.Based on the information from GLOBOCAN 2018 data, approximately 2.09 million new cases and 1.76 million deaths are reported each year[1]. Lung cancer ranks among the most prevalent malignant neoplasms in China. The 2015 data published by the National Cancer Center reveals that the 5-year prevalence rate of lung cancer in China during the period of 2006 to 2011 stood at 130.2 cases per 100,000 individuals.Of these cases, the prevalence rate for men was 84.6 (1/100 000), ranking second for malignant tumors, while the rate for women was 45.6 (1/100 000), ranking fourth for malignant tumors[2]. Histopathologically, lung malignancy can be categorized as small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC), with NSCLC accounting for approximately 80% of all cases based on histological analysis.Early-stage metastatic lung cancer can be treated by tumor resection but advanced or metastatic lung cancer still requires radiotherapy alone or in combination with chemotherapy[3]. Despite the recent development of innovative treatments, the survival rate of lung cancer patients is still only about 15% with late-stage disease manifestations, histological heterogeneity of the tumor subtypes, and resistance to anti-tumor drugs being the key reasons for poor prognosis[4]. Understanding the underlying mechanisms of lung cancer tumorigenesis is essential in enhancing patient diagnosis, treatment, and prognosis.
The body of research indicates that non-coding RNAs (ncRNAs) are significantly involved in the development and advancement of non-small cell lung cancer (NSCLC).[5–7]. MicroRNAs (miRNAs), comprising small ncRNAs with a length of 20–24 nucleotides, have emerged as key players in this context[8, 9]. They were first discovered in 1993 in Caenorhabditis elegans[10, 11]. Since then, miRNAs have been shown to have significant importance in the regulatory pathways of both unicellular and multicellular eukaryotes. Small RNA molecules have the ability to selectively identify and attach to matching regions found in the 3'-untranslated portions (UTRs) of target messenger RNAs. This interaction can impede translation or induce degradation of the mRNA, ultimately causing post-transcriptional gene silencing[12]. In addition, miRNAs can also activate gene expression under certain conditions either directly or indirectly. The miRBase database currently contains over 2500 mature miRNAs derived from 1188 miRNA precursors[13].
Thousands of miRNAs have been shown to be associated with various human diseases, including malignant tumors. In 2002, a study by Calin et al. showed a relationship between miRNA dysregulation and cancer[14]. In 2004, Takamizawa et al. demonstrated a relationship between miRNA expression and lung cancer[15]. miR-519d-3p has been found to inhibit the expression of Bcl-w and hypoxia-inducing factor (HIF)-1α, reducing hypoxia-induced tumorigenesis[16], while miR-487a-3p down-regulation inhibits the progression of NSCLC by targeting Smad7[17].
Janus kinase 2 (JAK2) serves as a non-receptor tyrosine kinase signaling molecule responsible for transducing the effects of a range of hormones and cytokines such as interferon, erythropoietin, leptin, and growth hormone.[18, 19]. JAK2 plays a critical role in the regulation of cellular volume, safeguarding cells during energy utilization and proliferation, and facilitating the survival of tumor cells. The JAK/STAT pathway is an evolutionarily conserved signaling pathway, involving many basic cell functions, such as cell growth and metastasis, which can lead to the development and progression of cancer[20].
In this study, we identified several miRNAs that are differentially expressed in lung cancer through data mining and the sorting of lung cancer gene chips (Accession No. GSE24709)[21]. Through tissue sample verification, we found that miR-618 showed low expression in NSCLC tissue cells. Our findings indicate that miR-618 specifically targets JAK2 within tumor cells, resulting in the suppression of migration and invasion in NSCLC cells by modulating the JAK2/STAT3 pathway, thus providing new insights into the pathogenesis of NSCLC.