LRRC75A‐AS1 delivered by M2 macrophage exosomes promotes cervical cancer progression via enhancing SIX1 expression

Abstract

AbstractWe aimed to investigate potential roles of LRRC75A‐AS1 delivered by M2 macrophage exosomes in inducing cervical cancer progression. We demonstrated LRRC75A‐AS1 was highly expressed in exosomes from M2 macrophages which could be absorbed by Hela cells. M2 macrophage‐derived exosomes promoted Hela cell proliferation, migration, invasion, and EMT process by delivering LRRC75A‐AS1. LRRC75A‐AS1 directly targeted and suppressed miR‐429 in Hela cells. The regulation of cell functions by exosomes from LRRC75A‐AS1‐overexpressing M2 macrophages was abrogated by miR‐429 mimics. miR‐429 directly targeted and repressed SIX1 expression. SIX1 overexpression alleviated the modulation of cellular functions and STAT3/MMP‐9 signaling by miR‐429 mimics. Also, miR‐429 overexpression or SIX1 silence repressed tumor formation and metastasis in nude mice, which was mitigated by exosomes from LRRC75A‐AS1‐overexpressing M2 macrophages. In conclusion, LRRC75A‐AS1 delivered by M2 macrophage exosomes repressed miR‐429 to elevate SIX1 expression and promote cervical cancer progression through activating the STAT3/MMP‐9 axis.