Role of Exosomal Noncoding RNAs in Lung Carcinogenesis

Table 1

The potential mechanisms and target genes of miRNAs in lung cancer.

Onco-miRNA	Potential mechanisms	Target genes	Reference
miR-21	Overexpression of miR-21 enhances tumorigenesis and inhibits apoptosis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis	PTEN, SPRY1, SPRY2, BTG2, PDCD4, APAF1, FasL, and RHOB	[42]
miR-212	Exert an antiapoptotic effect through direct repression of synaptic acetylcholinesterase expression in NSCLC	AChE	[60]
miR-17–92 cluster	Enhances cell proliferation, inhibits apoptosis, and protects against DNA damage	p21, CTGF, Tsp1, PTEN, Bim, and HIF-1α	[16, 61]
miR-221-222	Activates the PI3K/Akt; pathway and metallopeptidases	Kit, p27 kip1, PTEN/TIMP3, PUMA, and TRAIL	[62]
miR-93,; miR-98, and; miR-197	Inhibits tumor suppressor gene FUS1 expression	FUS1	[63]
miR-375	miR-375 upregulation and correlates with ASCL1 in the cell lines generated from mouse SCLC-like tumors	Not determined	[64]
miR-17-5p and; miR-20a	miRNA inhibition reduces cell growth; miRNA inhibition induces apoptosis and increases the proportions of sub-G1 populations	E2F1	[65]
miR-328	Associated with cell migration and NSCLC brain metastases by controlling the VEGF/IL1 signaling pathway	PRKCA, VEGF-D, NOTCH1, IL1-α, IL1-β, and PLC-γ	[66]
miR-106	Upregulated in lung cancer	RB	[67]
miR-155	Promotes cell proliferation through the repression of SOCS1; Downregulates several tumor suppressors such as PTEN, PDC4, and SHIP1, leading to the activation of the Akt pathway; Plays a role in cell invasion by targeting RhoA	CASP3, TP53BP1, SOCS1, PTEN, PDC4, and SHIP1	[68–70]
Tumor suppressor miRNA	Potential mechanisms	Target genes	Reference
let-7 family	Suppress cell proliferation by negatively regulating pathways promoting the G1 to S transition	KRAS, CDC25a, CDK6, c-MYC, CCND1, and BCL-2	[39, 71]
miR-126	Inhibits cell proliferation by arresting the cells in the G1 phase by targeting VEGF	VEGF, CRK, and SLC7A5,	[49, 72]
miR-26a	Inhibits cell proliferation, blocks G1/S phase transition, induces apoptosis, and inhibits cell metastasis and invasion in vitro	EZH2	[73]
miR-7	Involved in miR-7-mediated growth suppression and apoptosis; Inhibits cancer cell migration	BCL-2	[74]
miR-335	Reduces cell migration, invasion, proliferation, and metastasis	BCL-W and SP1	[75]
miR-145	Inhibits cell growth, proliferation, and migration of lung cancer cells and induces cell cycle arrest in G1 by targeting CDK4	EGFR, NUDT1, CDK4, c-Myc, and OCT4	[76–78]
miR-413	Inhibits cell proliferation and enhances apoptosis	PKC	[79]
miR-192	Inhibits cell proliferation and induces cell apoptosis in lung cancer cells; Arrests cells in G1 phase	RB1	[80]
miR-449 cluster	Induces apoptosis targeting Bcl-2, n-MYC, and HDAC1 and upregulates p53 through the repression of deacetylase gene SIRT1; Inhibits cell migration and invasion by suppression of AXL and SNAIL-1	CDK4, CDK6, c-MYC, CCND1, CCNE2, CDC25A, MET, and E2F	[81–83]
miR-206	Overexpression of miR-206 inhibits migration and invasion of lung cancer cells	Not determined	[84]
miR-146a	Inhibits cell growth and induces cell apoptosis; Suppresses motility; Enhances cell proliferation inhibitory effect of TKIs and cetuximab	EGFR	[85]
miR-203	Inhibits cell proliferation and migration of lung cancer	PKC	[86]
miR-205	Regulates epithelial to mesenchymal transition by targeting ZEB1 and SIP1	Not determined	[87]
miR-214	Regulates the acquired resistance to gefitinib via the PTEN/AKT pathway	PTEN	[88]