miR‐26a suppresses autophagy in swine Sertoli cells by targeting <scp>ULK</scp>2

Ran, Maoliang; Li, Z; Cao, Rong; Wang, Bo; Fu, Peng; He, Chao; Chen, B

doi:10.1111/rda.13177

Cited by 17 publications

(6 citation statements)

References 43 publications

(52 reference statements)

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“…Specifically, mir-26a avoids autophagy in two ways. The first one is through Beclin-1 mRNA interaction (57) and the second one is binding to mRNA of ULK1/ULK2 (58)(59)(60). Nevertheless, the effect of autophagy repression is controversial; it can act as a suppressor of cancer progression or in the maintenance of several traits of tumoral phenotype.…”

Section: Discussionmentioning

confidence: 99%

Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1α

et al. 2021

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Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide in both sexes. Current therapies include surgery, chemotherapy, and targeted therapy; however, prolonged exposure to chemical agents induces toxicity in patients and drug resistance. So, we implemented a therapeutic strategy based on the combination of doxorubicin, metformin, and sodium oxamate called triple therapy (Tt). We found that Tt significantly reduced proliferation by inhibiting the mTOR/AKT pathway and promoted apoptosis and autophagy in CRC derived cells compared with doxorubicin. Several autophagy genes were assessed by western blot; ULK1, ATG4, and LC3 II were overexpressed by Tt. Interestingly, ULK1 was the only one autophagy-related protein gradually overexpressed during Tt administration. Thus, we assumed that there was a post-transcriptional mechanism mediating by microRNAs that regulate UKL1 expression during autophagy activation. Through bioinformatics approaches, we ascertained that ULK1 could be targeted by mir-26a, which is overexpressed in advanced stages of CRC. In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1α transcription factor recognition sites. We developed two different HIF-1α stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1α enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1α detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1α and that in turn regulates mir-26a transcription.

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Section: Discussionmentioning

confidence: 99%

Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1α

et al. 2021

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“…Interestingly, while PAK2 is one target gene of miR-26a, another miR-26a target gene, ULK2 , was also a testis-associated gene in our study. ULK2 , when knocked down, will inhibit swine Sertoli cell autophagy (Ran et al, 2018a). Meanwhile the testis-specific genes identified in this study such as SPEM1 , TNP1 , PRM1 , DAZL (Hashemi et al, 2018), and CABYR (Shen et al, 2019) were also published as specific expression in human or mouse.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Profiles of mRNAs and miRNAs Reveal Molecular Characteristics of Multiple Organ Physiologies and Development in Pigs

et al. 2019

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The pig (Sus scrofa) is not only an important livestock animal but also widely used as a biomedical model. However, the understanding of the molecular characteristics of organs and of the developmental skeletal muscle of the pig is severely limited. Here, we performed a comprehensive transcriptome profiling of mRNAs and miRNAs across nine tissues and three skeletal muscle developmental stages in the Guizhou miniature pig. The reproductive organs (ovary and testis) had greater transcriptome complexity and activity than other tissues, and the highest transcriptome similarity was between skeletal muscle and heart (R = 0.79). We identified 1,819 mRNAs and 96 miRNAs to be tissue-specific in nine organs. Testis had the largest number of tissue-specific mRNAs (992) and miRNAs (40). Only 15 genes and two miRNAs were specifically expressed in skeletal muscle and fat, respectively. During postnatal skeletal muscle development, the mRNAs associated with focal adhesion, Notch signaling, protein digestion, and absorption pathways were up-regulated from D0 to D30 and then down-regulated from D30 and D240, while genes with opposing expression patterns were significantly enriched in the oxidative phosphorylation and proteasome pathways. The miRNAs mainly regulated genes associated with insulin, Wnt, fatty acid biosynthesis, Notch, MAPK, TGF-beta, insulin secretion, ECM–receptor interaction, focal adhesion, and calcium signaling pathways. We also identified 37 new miRNA–mRNA interaction pairs involved in skeletal muscle development. Overall, our data not only provide a rich resource for understanding pig organ physiology and development but also aid the study of the molecular functions of mRNA and miRNA in mammals.

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“…MiR26a has the same seed sequence with the miR26b and has been re ported as a tumor suppressor in liver cancer cells [7,8], osteosarcoma cells [9] and papillary thyroid cancer cells [10]. Studies have also shown that miR26a regulates the os teogenic differentiation of bone marrow mesenchymal stem cells [11], the proliferation of mouse hepatocyte [12], the apoptosis of endothelial cells [13] and the autophagy of swine Sertoli cells [14]. However, the regulation mechanism of miR26a in ovarian function and follicular development is still rarely reported.…”

Section: Introductionmentioning

confidence: 99%

MiR-26a promotes apoptosis of porcine granulosa cells by targeting the 3β-hydroxysteroid-Δ24-reductase gene

Zhang

Tao

Shang

et al. 2020

Asian-Australas J Anim Sci

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Objective: Apoptosis of ovarian granulosa cells (GCs) affects mammalian follicular development and fecundity. This study aimed to explore the regulatory relationship between microRNA-26a (miR-26a) and the 3β-hydroxysteroid-Δ24-reductase gene (DHCR24) gene in porcine follicular granular cells (pGCs), and to provide empirical data for the development of methods to improve the reproductive capacity of pigs.Methods: The pGCs were transfected with miR-26a mimic, miR-26a inhibitor and DHCR24-siRNA in vitro. The cell apoptosis rate of pGCs was detected by the flow cytometry. The secretion levels of estradiol (E2) and progesterone (P) in pGCs were detected by enzymelinked immunosorbent assay. Double luciferase validation system was used to detect the binding sites between miR-26a and DHCR24 3′-UTR region. Qualitative real-time polymerase chain reaction and Western blotting were used to verify the DHCR24 mRNA and protein expression in pGCs, respectively, after transfecting with miR-26a mimic and miR-26a inhibitor.Results: Results showed that enhancement of miR-26a promoted apoptosis, and inhibited E2 and P secretion in pGCs. Meanwhile, inhibition of DHCR24 also upregulated the Caspase-3 expression, reduced the BCL-2 expression, promoted pGCs apoptosis, and inhibited E2 and P secretion in pGCs. There were the binding sites of miR-26a located within DHCR24 3′-UTR. Up-regulation of miR-26a inhibited DHCR24 mRNA and protein expression in pGCs.Conclusion: This study demonstrates that miR-26a can promote cell apoptosis and inhibit E2 and P secretion by inhibiting the expression of DHCR24 in pGCs.

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miR‐26a suppresses autophagy in swine Sertoli cells by targeting ULK2

Cited by 17 publications

References 43 publications

Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1α

Combination of Metformin, Sodium Oxamate and Doxorubicin Induces Apoptosis and Autophagy in Colorectal Cancer Cells via Downregulation HIF-1α

Comprehensive Profiles of mRNAs and miRNAs Reveal Molecular Characteristics of Multiple Organ Physiologies and Development in Pigs

MiR-26a promotes apoptosis of porcine granulosa cells by targeting the 3β-hydroxysteroid-Δ24-reductase gene

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