scholarly journals Leptin Gene Protects Against Cold Stress in Antarctic Toothfish

2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Wang ◽  
Huamin Wang ◽  
Linghong Hu ◽  
Liangbiao Chen
Keyword(s):  
Cold Stress ◽  
Disulfide Bonds ◽  
Cold Treatment ◽  
Rapid Evolution ◽  
Protective Role ◽  
Mrna Levels ◽  
Antarctic Toothfish ◽  
Over Expression ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Leptin is a cytokine-like peptide, predominantly biosynthesized in adipose tissue, which plays an important role in regulating food intake, energy balance and reproduction in mammals. However, how it may have been modified to enable life in the chronic cold is unclear. Here, we identified a leptin-a gene (lepa) in the cold-adapted and neutrally buoyant Antarctic toothfish Dissostichus mawsoni that encodes a polypeptide carrying four α-helices and two cysteine residues forming in-chain disulfide bonds, structures shared by most vertebrate leptins. Quantitative RT-PCR confirmed that mRNA levels of the leptin-a gene of D. mawsoni (DM-lepa) were highest in muscle, followed by kidney and liver; detection levels were low in the gill, brain, intestine, and ovary tissues. Compared with leptin-a genes of fishes living in warmer waters, DM-lepa underwent rapid evolution and was subjected to positive selection. Over-expression of DM-lepa in the zebrafish cell line ZFL resulted in signal accumulation in the cytoplasm and significantly increased cell proliferation both at the normal culture temperature and under cold treatment. DM-lepa over-expression also reduced apoptosis under low-temperature stress and activated the STAT3 signaling pathway, in turn upregulating the anti-apoptotic proteins bcl2l1, bcl2a, myca and mdm2 while downregulating the pro-apoptotic baxa, p53 and caspase-3. These results demonstrate that DM-lepa, through STAT3 signaling, plays a protective role in cold stress by preventing apoptotic damage. Our study reveals a new role of lepa in polar fish.

scholarly journals THAP9-AS1 Promotes Tumorigenesis and Reduces ROS Generation through the JAK2/STAT3 Signaling Pathway by Increasing SOCS3 Promoter Methylation in Osteosarcoma

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Shuai Yang ◽  
Bing Wang ◽  
Chang Liu ◽  
Qizun Wang ◽  
Ronghuan Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Ectopic Expression ◽  
Dna Methyltransferases ◽  
Migration And Invasion ◽  
Ros Generation ◽  
Mrna Levels ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Comparison Results

Increasing studies have demonstrated that dysfunction of long noncoding RNAs (lncRNAs) plays critical roles in the development of human cancers. THAP9-AS1 has been reported to be dysregulated and associated with tumor progression in some cancers. However, the function and mechanism of THAP9-AS1 in osteosarcoma (OS) remain unclear. In the present study, we found that the expression of THAP9-AS1 was significantly upregulated in OS tissues and associated with the advanced stage of tumors and poor prognosis of patients. Blast comparison results showed that the SOCS3 promoter region and THAP9-AS1 had base complementary pairing binding sites. The interactions between THAP9-AS1, DNA methyltransferases (DNMTs), and SOCS3 were assessed by RIP and ChIP assays. The results of methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) validated that THAP9-AS1 enhanced the methylation level of the SOCS3 promoter. The mRNA levels of SOCS3 in OS cells could be reversed by the demethylation agent 5-aza-2 ′ -deoxycytidine. The mRNA expression of SOCS3 was downregulated in OS tissues and negatively correlated with THAP9-AS1 expression in tumors. Moreover, the western blot and immunofluorescence (IF) assay data showed that THAP9-AS1 activated the JAK2/STAT3 signaling pathway by upregulating p-JAK2 and p-STAT3 and the nuclear translocation of p-STAT3. Functionally, ectopic expression of THAP9-AS1 promoted cell proliferation, migration, and invasion and inhibited apoptosis, and this phenomenon could be reversed by SOCS3. Introduction of the JAK/STAT inhibitor AG490 partially abolished the stimulative effect of THAP9-AS1 on cellular processes. In addition, THAP9-AS1 decreased oxidative stress by reducing reactive oxygen species (ROS) and enhancing the mitochondrial membrane potential of OS cells via the SOCS3/JAK2/STAT3 pathway. Stable overexpression of THAP9-AS1 contributed to tumor growth and metastasis in vivo. In total, our findings suggested that upregulation of THAP9-AS1 might recruit DNMTs to epigenetically inhibit SOCS3, thereby activating the JAK2/STAT3 signaling pathway and oncogenesis of OS. These results provide novel insights for the understanding of OS progression.

scholarly journals MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zheng Zheng ◽  
Yan Chen ◽  
Yinzhou Wang ◽  
Yongkun Li ◽  
Qiong Cheng
Keyword(s):  
Cell Death ◽  
Intracranial Aneurysm ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Control Group ◽  
Type I ◽  
Mrna Levels ◽  
Reporter Assay ◽  
Over Expression ◽  
Tnf Α

AbstractCollagen-type I alpha 1 chain (COL1A1) and COL1A2 are abnormally expressed in intracranial aneurysm (IA), but their mechanism of action remains unclear. This study was performed to investigate the mechanism of COL1A1 and COL1A2 affecting the occurrence and rupture of IA. Quantitative real-time polymerase chain reaction was used to measure the expression of hsa-miR-513b-5p, COL1A1, COL1A2, TNF-α, IL-6, MMP2, MMP3, MMP9 and TIMP4 in patients with ruptured IA (RA) (n = 100), patients with un-ruptured IA (UA) (n = 100), and controls (n = 100). Then, human vascular smooth muscle cells (HASMCs) were cultured, and dual luciferase reporter assay was performed to analyse the targeting relationship between miR-513b-5p and COL1A1 or COL1A2. The effects of the miR-513b-5p mimic and inhibitor on the proliferation, apoptosis, and death of HASMC and the RIP1-RIP3-MLKL and matrix metalloproteinase pathways were also explored. The effect of silencing and over-expression of COL1A1 and COL1A2 on the role of miR-513b-5p were also evaluated. Finally, the effects of TNF-α on miR-513b-5p targeting COL1A1 and COL1A2 were tested. Compared with those in the control group, the serum mRNA levels of miR-513b-5p, IL-6 and TIMP4 were significantly decreased in the RA and UA groups, but COL1A1, COL1A2, TNF-α, IL-1β, MMP2, MMP3 and MMP9 were significantly increased (p < 0.05). Compared with those in the UA group, the expression of COL1A1, COL1A2, TNF-α, IL-1β and MMP9 was significantly up-regulated in the RA group (p < 0.05). Results from the luciferase reporter assay showed that COL1A1 and COL1A were the direct targets of miR-513b-5p. Further studies demonstrated that miR-513b-5p targeted COL1A1/2 to regulate the RIP1-RIP3-MLKL and MMP pathways, thereby enhancing cell death and apoptosis. Over-expression of COL1A1 or COL1A2, rather than silencing COL1A1/2, could improve the inhibitory effect of miR-513b-5p on cell activity by regulating the RIP1-RIP3-MLKL and MMP pathways. Furthermore, over-expression of miR-513b-5p and/or silencing COL1A1/2 inhibited the TNF-α-induced cell proliferation and enhanced the TNF-α-induced cell death and apoptosis. The mechanism may be related to the inhibition of collagen I and TIMP4 expression and promotion of the expression of RIP1, p-RIP1, p-RIP3, p-MLKL, MMP2 and MMP9. MiR-513b-5p targeted the inhibition of COL1A1/2 expression and affected HASMC viability and extracellular mechanism remodelling by regulating the RIP1-RIP3-MLKL and MMP pathways. This process might be involved in the formation and rupture of IA.

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