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microRNA-6785-5p-loaded human umbilical cord mesenchymal stem cells-derived exosomes suppress angiogenesis and metastasis in gastric cancer via INHBA.

Life Sciences 2021 November 2
OBJECTIVE: Exosomes (Exos) are known to transfer microRNAs (miRNAs) to participate in human diseases. We aim to identify the role of human umbilical cord mesenchymal stem cells (HUCMSCs)-derived Exos (HUCMSC-Exos) conveying miR-6785-5p in gastric cancer (GC).

METHODS: MiR-6785-5p and inhibin subunit beta A (INHBA) expression in GC tissues and cells were determined. GC cells were transfected with the vectors that altered miR-6785-5p or INHBA expression. HUCMSCs were transfected with altered miR-6785-5p or INHBA vectors, and the HUCMSC-Exos were extracted. Then, HUCMSC-Exos were co-cultured with GC cells. The proliferation, migration, invasion, apoptosis and angiogenesis of GC cells were assessed. The binding relationship between miR-6785-5p and INHBA was verified.

RESULTS: MiR-6785-5p was down-regulated and INHBA was up-regulated in GC tissues and cells. Elevation of miR-6785-5p or inhibition of INHBA restricted the malignant development of GC cells. HUCMSC-Exos suppressed malignant episodes of GC cells, which could be further enhanced by up-regulated miR-6785-5p or down-regulated INHBA. Elevated INHBA abolished the impacts of up-regulated miR-6785-5p in HUCMSC-Exos on GC cells. INHBA was confirmed as a target gene of miR-6785-5p.

CONCLUSION: HUCMSC-Exos containing elevated miR-6785-5p suppress angiogenesis and metastasis in GC via inhibiting INHBA. This study may further the understanding on molecular mechanisms of GC.

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