Abstract
MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are components of many signaling pathways associated with tumor aggressiveness and cancer metastasis. Some lncRNAs are classified as competitive endogenous RNAs (ceRNAs) that bind to specific miRNAs to prevent interaction with target mRNAs. Studies have shown that the hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-Met) pathway is involved in physiological and pathological processes such as cell growth, angiogenesis, and embryogenesis. Overexpression of c-Met can lead to sustained activation of downstream signals, resulting in carcinogenesis, metastasis, and resistance to targeted therapies. In this review, we evaluated the effects of anti-oncogenic and oncogenic non-coding RNAs (ncRNAs) on c-Met, and the interactions among lncRNAs, miRNAs, and c-Met in cancer using clinical and tissue chromatin immunoprecipition (ChIP) analysis data. We summarized current knowledge of the mechanisms and effects of the lncRNAs/miR-34a/c-Met axis in various tumor types, and evaluated the potential therapeutic value of lncRNAs and/or miRNAs targeted to c-Met on drug-resistance. Furthermore, we discussed the functions of lncRNAs and miRNAs in c-Met-related carcinogenesis and potential therapeutic strategies.
Highlights
Mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase that belongs to the MET (MNNG HOS transforming gene) family (Salgia, 2017)
A previous study has attempted to explain that long non-coding RNAs (lncRNAs)-MIR22HG played a tumor suppressive role through dysregulation of the oncogenes YBX1, MET, and p21, which resulted in reduced cell survival and increased cell death signaling in human primary lung tumors (Su et al, 2018)
Many studies have focused on lncRNAs, including lnc-X-Inactive Specific Transcript (XIST), lnc-MALAT1, lnc-GAPLINC, lnc-HOTAIR, and lnc-ARSR, as competitive endogenous RNAs (ceRNAs) targeting to miR-34 (Figure 1D)
Summary
Mesenchymal-epithelial transition factor (c-Met) is a receptor tyrosine kinase that belongs to the MET (MNNG HOS transforming gene) family (Salgia, 2017). Mutations, overexpression, or amplification of the MET gene in some tumor types resulted in aberrant HGF/c-Met axis activity, which induced cell motility and proliferation, promoted tumor development, and led to resistance to radiotherapy and targeted drug therapy in multiple cancers (Minuti et al, 2012; Barrow-Mcgee et al, 2016; Bahrami et al, 2017). MiRNAs regulate mRNA expression through degradation or silencing of mRNAs, while lncRNAs activate and repress genes via diverse mechanisms at the transcriptional or post-translational levels. Studies have shown that c-Met is a target gene of multiple miRNAs (Tables 1, 2) that play critical roles in controlling HGF/c-Met activity. Studies have shown that miR-34a suppressed cell growth, migration, and invasion, and increased cellular apoptosis and caspase activity by targeting c-Met in HCC cells (Dang et al, 2013). Inhibits cell growth and induced apoptosis; overcomes HGF-mediated gefitinib resistance Extends recurrence-free survival of patients Inhibits cell cycle progression, proliferation, and migration Inhibits cell proliferation, cell cycle progression, cell survival, and cell invasion Drives acute and late stages of radiation-induced fibrosis Induces apoptosis and cell cycle arrest; suppresses tumor growth Inhibits proliferation and metastasis Inhibits proliferation, invasion, and tumorigenicity; induces apoptosis Suppresses cell growth, migration, and invasion; increases cellular apoptosis and caspase activity Modulates proliferation and apoptosis in vivo; enhances cisplatin sensitivity in vitro Attenuates proliferation, invasion, and metastasis Inhibits growth, invasion, and metastasis
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