MiR-495 Regulates Cell Proliferation and Apoptosis in HO Stimulated Rat Spinal Cord Neurons Through Targeting Signal Transducer and Activator of Transcription 3 (STAT3)

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2021 Apr 14

PMID 33850858

Citations 3

Authors

Yunfeng Qiu

Ziru Zhao

Qi Chen

Bin Zhang

Chuanjun Yang

Affiliations

Soon will be listed here.

Abstract

Background: MicroRNA-495 (miR-495) is a post-translational modulator that performs several functions, and it is involved in several disease states. On the other hand, the physiological functions of miR-495 in HO stimulated mouse spinal cord neuronal dysfunction have not yet been fully understood.

Methods: In this study, we speculated that miR-495 may regulate the expression of STAT3 in the processes of neuronal proliferation and apoptosis following spinal cord injury (SCI). Cell viability was assessed with methyl thiazolyl tetrazolium (MTT) assay. Caspase-3 activity was assayed with ELISA. Cellular apoptotic changes were measured with TUNEL assay. Intracellular ROS production was determined by measuring uptake of dichlorodihydrofluorescein diacetate (DCFH-DA; PCR was used to assay the mRNA expression of STAT3 gene bearing predicted targeting positions for miR-495, while qRT-PCR was used to measure miR-495 mRNA.

Results: The results demonstrated that treatment of SCNs with HO led to a significant decrease in cell survival, while it enhanced apoptosis. The HO treatment induced cell membrane dysfunction, and increased ROS levels and DNA damage. Interestingly, the expression of miR-495 was markedly suppressed when SCNs were exposed to HO. However, miR-495 overexpression reversed HO-induced cytotoxicity and apoptosis in SCNs. Moreover, HO exposure elevated protein and mRNA concentrations of STAT3 in SCNs. Bioinformatics analysis showed likely binding domains of miR-495 in the 3'-untranslated regions of STAT3 in SCNs. MiR-495 loss-of-function and gain-of-function significantly up-regulated and down-regulated both STAT3 mRNA and protein expressions, respectively, in SCNs.

Conclusions: miR-495 overexpression inhibited HO-induced SCN dysfunction. This mechanism was mediated through the down-regulation of STAT3 expression.

Citing Articles

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