Table 2.

Summary of the in vivo studies defining the role of miR-218 in lung cancer

Model/Experimental design	Treatment groups	Timeline/Endpoint	Key findings	References
Intracardiac injection of metastatic NSCLC cells with tetracycline-inducible pri-miR-218; SCID mice	Doxycycline vs. control; pri-miR-218 ON/OFF	Metastasis was monitored at approximately 4 weeks; and survival was followed until endpoints	miR-218 overexpression reduced metastatic burden and improved survival	[76]
Subcutaneous xenografts using A549 cells with RPTPα mutation ± miR-218 modulation; BALB/c nude mice (n = 4/group)	A549-RPTPα mutation ± miR-218 manipulation	Tumor growth was monitored every 2 days starting at week 2, with the endpoint at approximately 5 weeks	miR-218 suppressed RPTPα expression and inhibited tumorigenesis	[78]
Subcutaneous xenografts with H1975 cells stably overexpressing miR-218; nude mice (n = 10/group)	miR-218 mimic vs. control	Tumors were measured on days 7, 9, 11, and 13; and the animals were sacrificed thereafter	miR-218 overexpression suppressed NSCLC xenograft growth	[73]
H1299 and A549 cell lines were injected into the posterior flanks; BALB/c nude mice (n = 6)	miR-218 overexpression vs. NC; anti-miR-218 vs. anti-NC	Tumors were measured every 2 days after Day 12, and the animals were sacrificed after Day 22	Overexpression of miR-218 suppressed Slug and ZEB2 expression and inhibited tumor growth and metastasis	[83]
Orthotopic lung implantation of tumor fragments from subcutaneous xenografts; BALB/c nude mice	miR-218 overexpression vs. control	Tumor growth and metastasis were assessed 7 weeks post-implantation
Subcutaneous A549 xenografts; BALB/c nude mice (n = 5/group)	miR-218-LV vs. control-LV	Tumor volume was measured weekly, and the animals were sacrificed at week 5 post-injection	miR-218 overexpression inhibited tumor growth by targeting STAT3	[56]
Subcutaneous xenografts using A549 cells; 10 BALB/c nude mice (n = 8)	miR-218 inhibitor vs. control	Tumor volume was measured every other day after reaching 50mm3, with the endpoint at 30 days	miR-218 inhibition promoted NSCLC xenograft growth	[79]
Subcutaneous A549R xenografts; BALB/c nude mice (n = 3/group)	miRNA-NC, miR-218 mimic; each ± 12 Gy X-ray	Tumor volume was measured every 3 days, with the endpoint at 25 days	miR-218–5p increased radiosensitivity in vivo	[91]

NSCLC: Non-small-cell lung cancer; RPTPα: receptor protein tyrosine phosphatase alpha; ZEB2: zinc finger E-box-binding homeobox 2; STAT3: signal transducer and activator of transcription 3; SCID: severe combined immunodeficient; NC: negative control; LV: lentivirus.