LINC00943 acts as miR-338-3p sponge to promote MPP+-induced SK-N-SH cell injury by directly targeting SP1 in Parkinson’s disease

Abstract

BackgroundAbnormal expression of long non-coding RNA (lncRNA) is associated with the progression of Parkinson’s disease (PD). LINC00943 has been proved to play an important role in the development of PD, so its role and mechanism in PD progression are worth further exploration. MethodsMPTP was used to construct PD mice model, and its active ingredient MPP+ was used to construct PD cell model. Cell proliferation and apoptosis were determined by MTT assay, EdU staining and flow cytometry. The protein levels of Cyclin D1, Bcl-2 and specificity protein 1 (SP1) were tested by western blot analysis. The concentrations of inflammation factors were examined by ELISA assay. The expression levels of LINC00943, microRNA (miR)-338-3p and SP1 were measured using quantitative real-time PCR. The interaction between miR-338-3p and LINC00943 or SP1 was confirmed using dual-luciferase reporter assay and RIP assay. ResultsOur data showed that LINC00943 was highly expressed in the brain tissues of MPTP-treated mice and MPP+-induced SK-N-SH cells. Knockdown of LINC00943 could promote the proliferation, while inhibit the apoptosis and inflammation of MPP+-induced SK-N-SH cells to alleviate cell injury. In terms of mechanism, we pointed out that LINC00943 could sponge miR-338-3p, and miR-338-3p could target SP1. The negative regulation of si-LINC00943 on MPP+-induced SK-N-SH cell injury could be reversed by miR-338-3p inhibitor. Moreover, miR-338-3p had a protective effect on SK-N-SH cells from MPP+-induced injury, which could be reversed by SP1 overexpression. Additionally, we confirmed that LINC00943 positively regulated SP1 via sponging miR-338-3p. ConclusionTo sum up, our data revealed that knockdown LINC00943 might alleviate PD progression through regulating the miR-338-3p/SP1 axis.