Hypoxia-induced miR-92a regulates p53 signaling pathway and apoptosis by targeting calcium-sensing receptor in genetically improved farmed tilapia (Oreochromis niloticus)

Abstract

miR-92a miRNAs are immune molecules that regulate apoptosis (programmed cell death) during the immune response. Apoptosis helps to maintain the dynamic balance in tissues of fish under hypoxia stress. The aim of this study was to explore the role and potential mechanisms of miR-92a in the liver of tilapia under hypoxia stress. We first confirmed that CaSR (encoding a calcium-sensing receptor) is a target gene of miR-92a in genetically improved farmed tilapia (GIFT) using luciferase reporter gene assays. In GIFT under hypoxia stress, miR-92a was up-regulated and CaSR was down-regulated in a time-dependent manner. Knocked-down CaSR expression led to inhibited expression of p53, TP53INP1, and caspase-3/8, reduced the proportion of apoptotic hepatocytes, and decreased the activity of calcium ions induced by hypoxia in hepatocytes. GIFT injected in the tail vein with an miR-92a agomir showed up-regulation of miR-92a and down-regulation of CaSR, p53, TP53INP1, and caspase-3/8 genes in the liver, resulting in lower serum aspartate aminotransferase and alanine aminotransferase activities under hypoxia stress. These findings suggest that stimulation of miR-92a interferes with hypoxia-induced apoptosis in hepatocytes of GIFT by targeting CaSR, thereby alleviating liver damage. These results provide new insights into the adaptation mechanisms of GIFT to hypoxia stress.

Hypoxia promotes pancreatic cancer cell migration, invasion, and epithelial-mesenchymal transition via modulating the FOXO3a/ DUSP6/ERK axis

“…The main mediator of the biological function of hypoxia, HIF-1α, is a chief controller of oxygen homeostasis and can regulate multifarious cellular functions, such as cell proliferation, apoptosis, and A metastasis (23)(24)(25). A previous study also demonstrated that under hypoxic conditions, the enhancement in HIF-1α expression triggers hypoxia-mediated apoptosis by influencing the expression of downstream molecules (26). Hypoxia was also found to induce cancer metastasis by upregulated HIF-1α expression via promotion of EMT (27).…”

Role of the Hypoxic-Secretome in Seed and Soil Metastatic Preparation

“…This effect is mediated by the modulation of the activity of macrophages and dendritic cells, the suppression of liver-resident NK cells, and the induction of TGF-β expression [ 115 ]. Additionally, in 2020, miRNA92a (regulated by hypoxia through HIF1α) [ 116 ] was reported to be released by BMDCs recruited to the premetastatic niche in response to hypoxia. Once secreted, miRNA92a acts by inhibiting its target SMAD7, leading to increased TGFβ secretion by hepatic stellate cells.…”

The novel circRNA hsa_circ_0000038 inhibits the progression of hepatocellular carcinoma by sponging miR-92a-2-5p to regulate the p53/p21 proteins

“…Furthermore, MiR-92a is a widely studied microRNA, in particular, its role in in ammatory and cancer diseases. Several studies have shown that miR-92 promote the expression of numerous cancer genes and is involved in multiple classical cancerassociated pathways (16)(17)(18)(19)(20)(21)(22)(23)(24). MiR-92a promotes hepatocellular carcinoma cell proliferation and invasion by Recombinant Forehead Box Protein A2 (FOXA2) targeting (25).…”