MiR‐127 attenuates adipogenesis by targeting MAPK4 and HOXC6 in porcine adipocytes

Gao, Yun; Wang, Yingqian; Chen, Xiaochang; Peng, Ying; Chen, Fen-Fen; He, Yuelin; Pang, Wei; Yang, Gongshe; Yu, Taiyong

doi:10.1002/jcp.28660

Cited by 36 publications

(22 citation statements)

References 53 publications

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“…miRNA is a type of small molecular RNA with a length of ∼22 nucleotides that is highly conserved in evolution 18 . miRNAs bind completely or incompletely to target mRNAs to cause translation or degradation in the regulation of gene expression, affecting the biological characteristics of animals, plants and microorganisms 8,19,20 . In this study, we demonstrated a new molecular mechanism for the development of PC.…”

Section: Discussionmentioning

confidence: 99%

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

Chen

Meng

et al. 2020

Cell Death Dis

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Pancreatic cancer (PC) is a malignant tumor with a poor prognosis and high mortality. However, the biological role of miR-548t-5p in PC has not been reported. In this study, we found that miR-548t-5p expression was significantly decreased in PC tissues compared with adjacent tissues, and that low miR-548t-5p expression was associated with malignant PC behavior. In addition, high miR-548t-5p expression inhibited the proliferation, migration, and invasion of PC cell lines. Regarding the molecular mechanism, the luciferase reporter gene, chromatin immunoprecipitation (ChIP), and functional recovery assays revealed that YY1 binds to the miR-548t-5p promoter and positively regulates the expression and function of miR-548t-5p. miR-548t-5p also directly regulates CXCL11 to inhibit its expression. A high level of CXCL11 was associated with worse Tumor Node Metastasis (TNM) staging in patients with PC, enhancing proliferation and metastasis in PC cells. Our study shows that the YY1/miR-548t-5p/CXCL11 axis plays an important role in PC and provides a new potential candidate for the treatment of PC.

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Section: Discussionmentioning

confidence: 99%

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

Chen

Meng

et al. 2020

Cell Death Dis

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“…In adipose tissue, miRNAs have been found to play important roles in adipocyte differentiation [7] and lipid metabolism [8]. For instance, miR-127 was found to be a negative regulator of adipogenesis by targeting the genes encoding mitogen-activated protein kinase 4 (MKK4) and homeobox C6 (HOXC6) in porcine adipocytes [9], and miR-302a inhibited adipogenesis by interacting with the 3 UTR of peroxisome proliferator activated receptor gamma (PPARγ) mRNA [10].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed MicroRNAs and Their Potential Target Genes in Adipose Tissue from Pigs with Highly Divergent Backfat Thickness

Xing

Zhao

Liu

et al. 2020

Animals

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Fatty traits are very important in pig production. However, the role of microRNAs (miRNAs) in fat deposition is not clearly understood. In this study, we compared adipose miRNAs from three full-sibling pairs of female Landrace pigs, with high and low backfat thickness, to investigate the associated regulatory network. We obtained an average of 17.29 million raw reads from six libraries, 62.27% of which mapped to the pig reference genome. A total of 318 pig miRNAs were detected among the samples. Among them, 18 miRNAs were differentially expressed (p-value < 0.05, |log2fold change| ≥ 1) between the high and low backfat groups; 6 were up-regulated and 12 were down-regulated. Functional enrichment of the predicted target genes of the differentially expressed miRNAs, indicated that these miRNAs were involved mainly in lipid and carbohydrate metabolism, and glycan biosynthesis and metabolism. Comprehensive analysis of the mRNA and miRNA transcriptomes revealed possible regulatory relationships for fat deposition. Negatively correlated mRNA–miRNA pairs included miR-137–PPARGC1A, miR-141–FASN, and miR-122-5p–PKM, indicating these interactions may be key regulators of fat deposition. Our findings provide important insights into miRNA expression patterns in the backfat tissue of pig and new insights into the regulatory mechanisms of fat deposition in pig.

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“…Over-expression of miR-767-5p functions as a tumor drive through targeting MAPK4 in multiple myeloma [ 31 ]. miR-127 was found to target both MAPK4 and HOXC6, and promotes cell proliferation and decreases differentiation in porcine [ 32 ]. These indicate that the expression and functions of MAPK4 may vary depending on the cellular context.…”

Section: Discussionmentioning

confidence: 99%

MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer

Tian

Lou

Tian

et al. 2020

J Exp Clin Cancer Res

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Background Cervical cancer is one of the most common cancers among females worldwide and advanced patients have extremely poor prognosis. However, adverse reactions and accumulating resistance to radiation therapy require further investigation. Methods The expression levels of mitogen-activated protein kinase 4 (MAPK4) mRNA were analyzed by real-time PCR and its association with overall survival was analyzed using Kaplan-Mier method. Colony formation, immunofluorescence and western blotting were used to examine the effects of MAPK4 knockout or over-expression on cervical cancer cells after radiation treatment. Drug-sensitivity of cervical cancer cells to PARP1 inhibitors, olaparib or veliparib, was analyzed by CCK-8 cell viability assays, and the 50% inhibitory concentration (IC50) was quantified using GraphPad Prism. The functional effects of MAPK4 knockout on the sensitivity of cervical cancer to radiation treatment and PARP1 inhibitors were further examined using xenograft tumor mouse models in vivo. Results Cervical cancer patients with high MAPK4 mRNA expression have lower survival rate. After radiation treatment, the colony number of MAPK4 knockout cells was markedly reduced, and the markers for DNA double-chain breakage were significantly up-regulated. In addition, MAPK4 knockout reduced protein kinase B (AKT) phosphorylation, whereas its over-expression resulted in opposite effects. In MAPK4 KO cells with irradiation treatment, inhibition of AKT phosphorylation promoted DNA double-chain breakage. Constitutive activation of AKT (CA-AKT) increased the levels of phosphorylated-AKT (p-AKT), and DNA repair-related proteins, phosphorylated-DNA-dependent protein kinase (p-DNA-PK) and RAD51 recombinase (RAD51). Furthermore, MAPK4 knockout was found to affect the sensitivity of cervical cancer cells to poly ADP-ribose polymerase 1 (PARP1) inhibitors by activating the phosphorylation of AKT. Moreover, in vivo results demonstrated that MAPK4 knockout enhanced the sensitivity of cervical cancer to radiation and PARP1 inhibitors in mouse xenograft models. Conclusions Collectively, our data suggest that combined application of MAPK4 knockout and PARP1 inhibition can be used as therapeutic strategy in radiation treatment for advanced cervical carcinoma.

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MiR‐127 attenuates adipogenesis by targeting MAPK4 and HOXC6 in porcine adipocytes

Cited by 36 publications

References 53 publications

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

The YY1/miR-548t-5p/CXCL11 signaling axis regulates cell proliferation and metastasis in human pancreatic cancer

Identification of Differentially Expressed MicroRNAs and Their Potential Target Genes in Adipose Tissue from Pigs with Highly Divergent Backfat Thickness

MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer

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