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.