Background: Intramuscular fat (IMF) content is a vital parameter for assessing pork quality. Increasing evidence has shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism were further explored with respect to intramuscular preadipocyte proliferation and differentiation.Results: By porcine adipose tissue miRNA sequencing analysis, we found that miR-146a-5p is a potential regulator of porcine IMF adipogenesis. Further studies showed that miR-146a-5p mimics inhibited porcine intramuscular preadipocyte proliferation and differentiation, while the miR-146a-5p inhibitor promoted cell proliferation and adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate TGF-β signaling. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor-associated factor 6 (TRAF6) to weaken the AKT/mTORC1 signaling downstream of the TRAF6 pathway.Conclusions: MiR-146a-5p targets SMAD4 and TRAF6 to inhibit porcine intramuscular adipogenesis by attenuating TGF-β and AKT/mTORC1 signaling, respectively. These findings provide a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
Background: Intramuscular fat (IMF) content is a vital parameter to assess pork quality. Increasing evidences have shown that microRNAs (miRNAs) play an important role in regulating porcine IMF deposition. Here, a novel miRNA implicated in porcine IMF adipogenesis was found, and its effect and regulatory mechanism was further explored on the proliferation and differentiation of intramuscular preadipocytes.Results: By miRNAs sequencing analysis in porcine adipose tissues, we found that miR-146a-5p was a potential regulator of porcine IMF adipogenesis. Further study showed that miR-146a-5p mimics inhibited the proliferation of porcine intramuscular preadipocytes, but its inhibitor promoted cell proliferation. Interestingly, miR-146a-5p mimics also repressed preadipocyte differentiation, whereas its inhibitor promoted adipogenic differentiation. Mechanistically, miR-146a-5p suppressed cell proliferation by directly targeting SMAD family member 4 (SMAD4) to attenuate the TGF-β signal. Moreover, miR-146a-5p inhibited the differentiation of intramuscular preadipocytes by targeting TNF receptor associated factor 6 (TRAF6) to weaken the NF-κB signaling of the TRAF6 downstream pathway.Conclusions: MiR-146a-5p targeting SMAD4 and TRAF6 inhibited porcine intramuscular adipogenesis through attenuating TGF-β and NF-κB signals, respectively. These findings provided a novel miRNA biomarker for regulating intramuscular adipogenesis to promote pork quality.
BackgroundColon cancer is one of the common cancers, and its prognosis remains to be improved. The role of cuproptosis as a newly discovered form of cell death in the development of colon cancer has not been determined.MethodsBased on 983 colon cancer samples in the TCGA database and the GEO database, we performed a comprehensive genomic analysis to explore the molecular subtypes mediated by cuproptosis-related genes. Single-sample gene set enrichment analysis (ssGSEA) was utilized to quantify the relative abundance of each cell infiltrate in the TME. A risk score was established using least absolute shrinkage and selection operator regression (LASSO), and its predictive ability for colon cancer patients was verified to explore its guiding value for treatment.ResultsWe identified two distinct cuproptosis-related molecular subtypes in colon cancer. These two distinct molecular subtypes can predict clinicopathological features, prognosis, TME activity, and immune-infiltrating cells. A risk model was developed and its predictive ability was verified. Compared with patients in the high-risk score group, patients in the low-risk score group were characterized by lower tumor microenvironment score, higher stem cell activity, lower tumor mutational burden, lower microsatellite instability, higher sensitivity to chemotherapeutics, and better immunotherapy efficacy.ConclusionThis study contributes to understanding the molecular characteristics of cuproptosis-related subtypes. We demonstrate a critical role for cuproptosis genes in colon cancer s in the TME. Our study contributes to the development of individualized treatment regimens for colon cancer.
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