2.3 Lung cancer
Lung cancer is the leading cause of cancer-related deaths, non-small cell lung cancer (NSCLC) which has an aggressive clinical course, is the most common type of lung cancer, adenocarcinoma is the most common histologic subtype of NSCLC, and squamous cell is the second common subtype [51, 52].
MALAT1, H19, and MEG3 are highly expressed in lung cancer tissue and have been shown to be involved in all stages of lung cancer formation. They are also important markers for the diagnosis and prognosis of lung cancer. LncRNAs are crucial roles and lncRNA-miRNA interactions are the most prevalent synergistic effects in tumors [21]. MALAT1 is regarded as a predictive marker for lung adenocarcinoma and was one of the earliest genes related to lung cancer to be discovered. The majority of MALAT1 is found in nuclear speckles, where it interacts with a variety of transcription factors, chromatin modifiers, and RNA binding proteins (RBPs) to control both transcriptional and post-transcriptional gene expression[53]. Malat1 is an essential lncRNA implicated in tumor growth, invasion, and metastatic processes even though it is not necessitated for normal tissue growth and development[54]. By increasing MALAT1 stability and modifying it through m6A methylation, METTL3 promotes MALAT1 spongy binding to miR-1914-3p, which in turn promotes YAP expression and YAP-induced metastasis and invasion in NSCLC[55].
HOTAIR is linked to the formation of several tumors, and one of the mechanisms is that HOTAIR controls several downstream targets via different signaling pathways, which are linked to tumor cell motility, proliferation, angiogenesis, invasion, and drug resistance[56]. MiR-613 is downregulated by HOTAIR, that is an extremely low expression in NSCLC tissues, which facilitates NSCLC invasion and metastasis [57] and mediates NSCLC genesis. In NSCLC cells, miR-221 reduces HOTAIR expression and increases apoptosis[58]. By interacting with miR-149-5p, HOTAIR drives the emergence of cisplatin resistance in NSCLC [59]. HOTAIR also mediates miR-217/DACH1 signaling pathway regulating proliferation, migration, and invasion of lung cancer cells[60].
Other lncRNA-miRNA interactions have also been demonstrated to contribute to lung tumorigenesis. For instance, in a feedback loop formed by lnc ZEB1-AS1 and miR-409-3p/ZEB1, miR-409-3p functions as a regulatory bridge, is suppressed by lnc ZEB1-AS1 thereby upregulating ZEB1, which then binds to the lnc ZEB1-AS1 promoter regions to promote tumorigenesis[61]. Lnc GACAT1 expression is increased in NSCLC tissues and cell lines, spongiosely binds miR-422a and inactivates the YY1 transcription factor (YY1), which may be associated with poorer clinical outcomes for patients[62].
Other lncRNA-miRNA interactions mechanisms in lung cancer see in the table 1.