HIF‐1α‐Mediated miR‐623 Regulates Apoptosis and Inflammatory Responses of Nucleus Pulposus Induced by Oxidative Stress via Targeting TXNIP

Abstract

Excessive apoptosis and inflammatory responses of nucleus pulposus (NP) cells induced by oxidative stress contribute to intervertebral disc degeneration (IVDD). Though some microRNAs are associated with IVDD, the specific microRNA that can mediate apoptotic and inflammatory responses of NP cells induced by oxidative stress synchronously still needs further identification. Here, we find that microRNA-623 (miR-623) is downregulated in IVDD and its expression is regulated by hypoxia-inducible factor-1α (HIF-1α) under oxidative stress conditions. Mechanistically, HIF-1α is observed to promote miR-623 expression by directly binding to its promoter region (−1,994/−1,987 bp). Functionally, miR-623 is found to work as an intermediator in alleviating apoptosis and inflammatory responses of NP cells induced by oxidative stress via regulating thioredoxin-interacting protein (TXNIP) expression by directly targeting its 3 ′ -untranslated region (3 ′ -UTR). Thus, on elucidating the expression and functional mechanisms of miR-623, our study suggests that miR-623 can be a valuable therapeutic target for treating oxidative stress-induced IVDD.

Silencing ATF3 Might Delay TBHP-Induced Intervertebral Disc Degeneration by Repressing NPC Ferroptosis, Apoptosis, and ECM Degradation

“…We sought to identify the upstream regulators of ATF3. The differentially expressed miRNAs (DEMs) play a crucial role in the initiation and development of IDD by targeting key genes [ 19 – 22 ]. We reanalyzed the IDD-related GSE116726 dataset using the criteria of |log 2 FC | > log 2 6 and −log 10 ( adj .…”

“…As negative regulators of gene expression, miRNAs play critical roles in the pathological process of IDD [ 20 – 22 ]. Previous investigations revealed the involvement of miR-874-3p in the pathology of the progression of IDD [ 34 , 41 ].…”

“…MicroRNA (miRNA) expression is temporal, and dysregulation in their expression is a hallmark pathological feature of IDD [ 19 ]. Accumulating evidence from animal experiments has demonstrated that miRNAs have therapeutic potential in IDD diseases [ 20 – 22 ]. miRNAs are short noncoding RNAs (ncRNAs), approximately 21-24 nucleotides long, which negatively modulate target gene expression and its downstream signaling pathway by directly binding to their target genes' 3′-UTR (untranslated regions), thereby mediating NPC growth and apoptosis, inflammatory response, ECM metabolism, and oxidative stress [ 19 – 22 ].…”

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1β Induced Inflammatory Response in Intervertebral Disc Degeneration

“…Chronic in ammation in the IVDs is connected with IVDD pathophysiology through triggering irreversible structural and biochemical changes (e.g., extracellular matrix degradation, vascular and nerve innervation) [4,5]. Meanwhile, a few previous researches demonstrated that the miRNA could target the downstream gene to primarily a ecting in ammatory signal response, thus involving in the development and progression of IVDD [6,7].…”

Cochlear Marginal Cell Pyroptosis Is Induced by Cisplatin via NLRP3 Inflammasome Activation

“…UCA1 is an lncRNA that has been confirmed to play a role in cisplatin pharmacology by regulating Wnt/β-catenin, Mir-143/FOSL2, Mir-495/NRF2, and other pathways ( 81 – 83 ). TXNIP has also been reported to play different roles by binding to different microRNAs ( 84 – 86 ). However, these studies are piecemeal and have not yet formed a concrete network.…”