Multiple Sclerosis

OIP5-AS1[LncRNA]

miR-140-5p[miRNA]

RhoA[mRNA]

CD4(+)IL-17(+) cell

Homo sapiens (human)

Life Sci. 2021 Jan 27:119108. doi: 10.1016/j.lfs.2021.119108.

OIP5-AS1 facilitates Th17 differentiation and EAE severity by targeting miR-140-5p to regulate RhoA/ROCK2 signaling pathway.

ELISA;qPCR;RT-qPCR;Western blot;Flow Cytometry assay;Luciferase reporter assay;

AIMS: Multiple sclerosis (MS) is one of the commonest neurologic disorders globally. LncRNA OIP5-AS1 has been found to be implicated in the etiology of MS. This study was to explore the roles and molecular mechanisms of OIP5-AS1 in the development of MS. MATERIALS AND METHODS: RT-qPCR assay was used to measure expressions of OIP5-AS1, miR-140-5p, IL-17A mRNA and RhoA mRNA. CD4(+)IL-17(+) cell proportion was determined by flow cytometry. IL-17A secretion was examined by ELISA assay. Cell inflammatory infiltration and demyelination were assessed by histological analyses. The interaction between miR-140-5p and OIP5-AS1 or RhoA 3'UTR was validated by bioinformatical analysis and luciferase reporter assay. Western blot assay was performed to detect protein expressions of ROCK2 and RhoA. An experimental autoimmune encephalomyelitis (EAE) models was established to explore the role of OIP5-AS1 in MS in vivo. KEY FINDINGS: OIP5-AS1 expression was enhanced in MS patients. Also, elevated OIP5-AS1 level was observed during T-helper 17 (Th17) differentiation. Moreover, OIP5-AS1 promoted Th17 differentiation in vitro and contributed to the development of EAE in vivo. Mechanical explorations revealed that OIP5-AS1 targeted miR-140-5p to regulate Th17 differentiation. Moreover, RhoA was a target of miR-140-5p and miR-140-5p inhibited the activation of RhoA/ROCK2 signaling. Also, RhoA upregulation abrogated the inhibitory effects of miR-140-5p on Th17 differentiation. SIGNIFICANCE: OIP5-AS1 contributed to EAE development by targeting miR-140-5p/RhoA and activating RhoA/ROCK2 signaling pathway, shedding light on the roles and molecular mechanisms of OIP5-AS1 in the development of MS and providing some candidate targets for the diagnose and treatment of MS.