miR-199a-5p regulates the proliferation and apoptosis of degenerative nucleus pulposus cells through the CDKN1B/NF-κB axis

Abstract

Intervertebral disc degeneration is a multifactorial pathological disease. miR-199a-5p is exceedingly implicated in regulating degenerative nucleus pulposus cell (DNPC). We explored the roles of miR-199a-5p in DNPCs. Cell morphology and Collagen II-positive expression were observed. Cell proliferation, apoptosis, and Bax and Bcl-2 levels were assessed. miR-199a-5p inhibitor, pcDNA3.1-CDKN1B, or si-CDKN1B was transfected into DNPCs. miR-199a-5p and CDKN1B expressions were detected. The binding relationship between miR-199a-5p and CDKN1B was verified. DNPCs with silenced miR-199a-5p and CDKN1B were treated with PDTC. The nuclear factor-κB (NF-κB) pathway-related protein levels were detected. DNPCs showed decreased proliferation and promoted apoptosis. miR-199a-5p was highly expressed in DNPCs. miR-199a-5p knockdown increased DNPC proliferation and inhibited apoptosis. CDKN1B was repressed in DNPCs. miR-199a-5p targeted CDKN1B. CDKN1B knockdown partially abrogated the effects of miR-199a-5p inhibition on DNPC proliferation and apoptosis. In DNPCs, p65 was translocated to the nucleus, IκB protein phosphorylation level was increased, and the NF-κB pathway was activated. miR-199a-5p knockdown or CDKN1B overexpression repressed the NF-κB pathway activation. NF-κB pathway inhibitor promoted DNPC proliferation and inhibited apoptosis. Briefly, miR-199a-5p was upregulated in DNPCs. We discovered for the first time that miR-199a-5p silencing repressed the NF-κB pathway by promoting CDKN1B transcription, thus promoting DNPC proliferation and inhibiting apoptosis.

MiR‐199a‐5p enhances neuronal differentiation of neural stem cells and promotes neurogenesis by targeting Cav‐1 after cerebral ischemia

“…Second, it is unsurprising that a single miRNA may modulate a series of transcripts, and various miRNAs can modulate the same mRNA as well. Multiple target genes of miR‐199a‐5p have been identified, such as CDKN1B and Sirtuin‐1 41,42 . Thus, we cannot rule out the possibility of the participation of potential targets other than Cav‐1 in miR‐199a‐5p‐mediated endogenous neurogenesis.…”

“…Multiple target genes of miR-199a-5p have been identified, such as CDKN1B and Sirtuin-1. 41,42 Thus, we cannot rule out the possibility of the participation of potential targets other than Cav-1 in miR-199a-5p-mediated endogenous neurogenesis.…”