MiR-370-3p Regulates Adipogenesis through Targeting Mknk1.
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ABSTRACT:
SUBMITTER: Zhang P
PROVIDER: S-EPMC8619113 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MicroRNAs (miRNAs), a class of 22 nucleotide (nt) noncoding RNAs, negatively regulate mRNA posttranscriptional modification in various biological processes. Morphogenesis of skin hair follicles in cashmere goats is a dynamic process involving many key signaling molecules, but the associated cellular biological mechanisms induced by these key signaling molecules have not been reported. In this study, differential expression, bioinformatics, and Gene Ontology/Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on miRNA expression profiles of Inner Mongolian cashmere goats at 45, 55, and 65 days during the fetal period, and chi-miR-370-3p was identified and investigated further. Real-time fluorescence quantification (qRT-PCR), dual luciferase reporting, and Western blotting results showed that transforming growth factor beta receptor 2 (TGF-βR2) and fibroblast growth factor receptor 2 (FGFR2) were the target genes of chi-miR-370-3p. Chi-miR-370-3p also regulated the expression of TGF-βR2 and FGFR2 at mRNA and protein levels in epithelial cells and dermal fibroblasts. DNA staining, Cell Counting Kit-8, and fluorescein-labelled Annexin V results showed that chi-miR-370-3p inhibited the proliferation of epithelial cells and fibroblasts but had no effect on apoptosis. Cell scratch test results showed that chi-miR-370-3p promoted the migration of epithelial cells and fibroblasts. Chi-miR-370-3p inhibits the proliferation of epithelial cells and fibroblasts by targeting TGF-βR2 and FGFR2, thereby improving cell migration ability and ultimately regulating the fate of epithelial cells and dermal fibroblasts to develop the placode and dermal condensate, inducing hair follicle morphogenesis.
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Project description:miRNAs play a crucial part in multiple biological processes of cell proliferation, migration, apoptosis, and chemoresistance. In cancer, miRNAs can be divided into oncogenes or tumor suppressors on the basis of their functions in the carcinogenic process. The purpose of this study was to explore the roles and clinical diagnostic value of miR-370-3p in breast cancer. Our results demonstrated that miR-370-3p significantly promoted proliferation, metastasis, and stemness of breast cancer in vitro and in vivo. In particular, clinical data revealed that high expression of serum miR-370-3p and exosomal miR-370-3p from breast cancer patients was remarkably correlated with lymphatic metastasis and tumor node metastasis (TNM) stages. Mechanistically, miR-370-3p inhibited FBLN5 expression and activated the NF-κB signaling pathway to promote breast cancer cell proliferation, migration, and stemness. FBLN5 expression was significantly decreased in breast cancer cells and tumor tissues of breast cancer patients. Our research identified that miR-370-3p promoted breast cancer progression by inhibiting FBLN5 expression and activating the NF-κB signaling pathway. Serum exosomal miR-370-3p would provide a potential biomarker for the diagnosis of breast cancer.
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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor worldwide. Circular RNA (circRNA) is of great value in tumorigenesis progression. However, the mechanism of circFNDC3B in ESCC remains to be clarified.MethodsFirstly, the circular characteristics of circFNDC3B were evaluated by Actinomycin D and RNase R measurements. The functions of circFNDC3B in ESCC cells were examined by CCK-8, EdU and flow cytometry. Subsequently, the molecular mechanism of circFNDC3B was explained using luciferase reporter gene detection. Finally, we constructed xenograft model to prove the role of circFNDC3B in vivo.ResultsOur study revealed that circFNDC3B was more stable than its linear RNA and prominently upregulated in ESCC. Functional findings suggested that silencing of circFNDC3B reduced the proliferation and enhanced apoptosis of ESCC cells in vitro. Meanwhile, knockdown of circFNDC3B attenuated tumor progression in vivo. Next, miR-370-3p/miR-136-5p was discovered to bind circFNDC3B. miR-370-3p/miR-136-5p reversed the promotive effect on cell proliferation and the inhibitory effect on cell apoptosis of circFNDC3B. MYO5A was a downstream target of miR-370-3p/miR-136-5p. CircFNDC3B served as a sponge for miR-370-3p/miR-136-5p and alleviated the prohibitory effect of miR-370-3p/miR-136-5p on MYO5A, which accelerated ESCC progression.ConclusioncircFNDC3B positively adjusted the MYO5A expression via spongy miR-370-3p/miR-136-5p, hence achieving the cancer-promoting effect on ESCC. circFNDC3B was a prospective diagnosis marker for ESCC.
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Project description:PurposeEndometriosis, a gynecological disease, is difficult to be cured. Currently, to identify more potential biomarkers for the early diagnosis of endometriosis is urgently needed. Insulin like growth factor 2 (IGF2) has been revealed to correlate with endometriosis. This research aimed to further explore the role of IGF2 and its up-stream mechanism in endometriosis.MethodsPrimary ectopic endometrial stromal cells (EESCs) were extracted from ectopic endometrial tissues which were pathological endometrial tissues resected from three patients with II-III endometriosis. Primary normal endometrial stromal cells (NESCs) were extracted from normal endometrial tissues of two patients with grade III cervical dysplasia and one patient with uterine leiomyoma III. Four endometriotic cell lines (EEC145T, hEM15A, hEM5B2, and 12Z) and normal human endometrial epithelial cells (hEECs) were purchased. Cell proliferation, migration, and invasion were evaluated through functional assays. The molecular interaction between RNAs was investigated through mechanistic analyses.ResultsWe discovered that IGF2 was upregulated in purchased endometriotic cells and primary EESC. Suppression of IGF2 hampered cell proliferation, migration, and invasion. Furthermore, insulin-like growth factor 2 antisense RNA (IGF2-AS) was uncovered to positively regulate IGF2 expression and enhanced proliferative, migratory, and invasive abilities of endometriotic cells. Mechanistically, miR-370-3p was found to bind with IGF2-AS and IGF2. IGF2-AS competitively bind with miR-370-3p to upregulate IGF2. Furthermore, IGF2-AS was revealed to activate the PI3K/AKT/mTOR signaling pathway through targeting miR-370-3p/IGF2 axis.ConclusionIGF2-AS promotes endometriotic cell growth via regulating IGF2/miR-370-3p axis and further activating PI3K/AKT/mTOR signaling pathway.
| S-EPMC9790843 | biostudies-literature
Project description:Ovarian cancer is a kind of cancer from the female genital tract; the molecular mechanism still needs to be explored. lncRNA plays a vital role in tumorigenesis and development. Our aim was to identify oncogenic lncRNAs in ovarian cancer and explore the potential molecular mechanism. SNHG15 was initially identified by using GEO datasets (GSE135886 and GSE119054) and validated by tumor tissues and the cell line, identifying that SNHG15 was upregulated in ovarian cancer. Besides, high SNHG15 indicated poor prognosis in ovarian cancer. Furthermore, knockdown SNHG15 suppresses ovarian cancer proliferation and promotes apoptosis. Mechanistically, SNHG15 promotes proliferation through upregulated CDK6 via sponging miR-370-3p. Taken together, our findings emphasize the important role of SNHG15 in ovarian cancer, suggesting that SNHG15 may be a promising target for ovarian cancer.
| S-EPMC8560251 | biostudies-literature
Project description:The development of skeletal muscle is a highly ordered and complex biological process. Increasing evidence has shown that noncoding RNAs, especially long-noncoding RNAs (lncRNAs) and microRNAs, play a vital role in the development of myogenic processes. In this study, we observed that lncMyoD regulates myogenesis and changes myofiber-type composition. miR-370-3p, which is directly targeted by lncMyoD, promoted myoblast proliferation and inhibited myoblast differentiation in the C2C12 cell line, which serves as a valuable model for studying muscle development. In addition, the inhibition of miR-370-3p promoted fast-twitch fiber transition. Further analysis indicated that acyl-Coenzyme A dehydrogenase, short/branched chain (ACADSB) is a target gene of miR-370-3p, which is also involved in myoblast differentiation and fiber-type transition. Furthermore, our data suggested that miR-370-3p was sponged by lncMyoD. In contrast with miR-370-3p, lncMyoD promoted fast-twitch fiber transition. Taken together, our results suggest that miR-370-3p regulates myoblast differentiation and muscle fiber transition and is sponged by lncMyoD.
| S-EPMC8072939 | biostudies-literature
Project description:Background Thyroid cancer is the most common malignant tumor in the endocrine system. Papillary thyroid carcinoma (PTC) accounts for the vast majority of cases in this cancer. Recently, the vital role of circular RNA (circRNA) has been acknowledged in various cancers, and this study aimed to investigate the role of circ_0058124 and related mechanism of its action in PTC. Materials and Methods The expression of circ_0058124, miR-370-3p and LIM domain only (LMO4) was detected by qRT-PCR in tissue samples (PTC tissues or normal tissues, n=20) and cell lines (non-cancer cell line, Nthy-ori 3–1, and PTC cell lines, IHH-4 and TPC-1). For functional analysis, cell proliferation was investigated using CCK-8 assay and colony formation assay. Cell migration and invasion were determined using transwell assay, and cell migration was also assessed by wound healing assay. Cell apoptosis was monitored by flow cytometry assay. For mechanism analysis, the interaction between miR-370-3p and circ_0058124 or LMO4 predicted by the bioinformatics analysis was validated by dual-luciferase reporter assay or RIP assay. The effect of circ_0058124 on tumor growth in vivo was identified by establishing the Xenograft model. Results The expression of circ_0058124 was enhanced in PTC tissues and cells. Circ_0058124 knockdown inhibited viability, colony formation, migration and invasion and promoted apoptosis of PTC cells. Besides, circ_0058124 knockdown also blocked tumor growth in vivo. miR-370-3p was a target of circ_0058124, and circ_0058124 regulated the expression of LMO4, a target of miR-370-3p, by targeting miR-370-3p. Rescue experiments presented that miR-370-3p inhibition reversed the inhibitory effects of circ_0058124 knockdown on PTC development, and LMO4 overexpression reversed the effect of miR-370-3p restoration on PTC development. Conclusion Circ_0058124 promoted the development of PTC by mediating the miR-370-3p/LMO4 axis, and circ_0058124, functioned as an oncogene in PTC, might be used as a promising biomarker for PTC diagnosis and treatment.
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Project description:Human adipose-derived stem cells (hASCs) are a promising cell type for bone tissue regeneration. Circular RNAs (circRNAs) have been shown to play a critical role in regulating various cell differentiation and involve in mesenchymal stem cell osteogenesis. However, how circRNAs regulate hASCs in osteogenesis is still unclear. Herein, we found circ_0003204 was significantly downregulated during osteogenic differentiation of hASCs. Knockdown of circ_0003204 by siRNA or overexpression by lentivirus confirmed circ_0003204 could negatively regulate the osteogenic differentiation of hASCs. We performed dual-luciferase reporting assay and rescue experiments to verify circ_0003204 regulated osteogenic differentiation via sponging miR-370-3p. We predicted and confirmed that miR-370-3p had targets in the 3′-UTR of HDAC4 mRNA. The following rescue experiments indicated that circ_0003204 regulated the osteogenic differentiation of hASCs via miR-370-3p/HDAC4 axis. Subsequent in vivo experiments showed the silencing of circ_0003204 increased the bone formation and promoted the expression of osteogenic-related proteins in a mouse bone defect model, while overexpression of circ_0003204 inhibited bone defect repair. Our findings indicated that circ_0003204 might be a promising target to promote the efficacy of hASCs in repairing bone defects.
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Project description:Endothelial dysfunction and inflammatory immune response trigger dedifferentiation of vascular smooth muscle cells (SMCs) from contractile to synthetic phenotype and initiate arterial occlusion. However, the complex vascular remodeling process playing roles in arterial occlusion initiation is largely unknown. We performed bulk sequencing of small and messenger RNAs in a rodent arterial injury model. Bioinformatic data analyses reveal that six miRNAs are overexpressed in injured rat carotids as well as synthetic-type human vascular SMCs. In vitro cell-based assays show that four miRNAs (miR-130b-5p, miR-132-3p, miR-370-3p, and miR-410-3p) distinctly regulate the proliferation of and monocyte adhesion to the vascular SMCs. Individual inhibition of the four selected miRNAs strongly prevents the neointimal hyperplasia in the injured rat carotid arteries. Mechanistically, miR-132-3p and miR-370-3p direct the cell cycle progression, triggering SMC proliferation. Gene ontology analysis of mRNA sequencing data consistently reveal that the miRNA targets include gene clusters that direct proliferation, differentiation, and inflammation. Notably, bone morphogenic protein (BMP)-7 is a prominent target gene of miR-370-3p, and it regulates vascular SMC proliferation in cellular and animal models. Overall, this study first reports that the miR-370-3p/BMP-7 axis determines the vascular SMC phenotype in both rodent and human systems.
| S-EPMC9918535 | biostudies-literature
Project description:BACKGROUND:Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previously, we showed that miR-34a was less abundant in liver tissue from pigs with higher backfat thickness, compared to pigs with lower backfat thickness. The purpose of this present study was to explore the role of miR-34a in adipogenesis. RESULT:Bioinformatics analysis identified Acyl-CoA synthetase long chain family member 4 (ACSL4) as a putative target of miR-34a. Using a luciferase reporter assay, we verified that miR-34a binds the ACSL4 mRNA at the 3'UTR. To examine the role of the miR-34a-ACSL4 interaction in IMF deposition in the pig, mRNA and protein expression of the ACSL4 gene was measured in primary intramuscular preadipocytes transfected with miR-34a mimic and inhibitor. Our results showed that ACSL4 is expressed throughout the entire differentiation process in pig preadipocytes, similar to the lipogenesis-associated genes PPAR? and aP2. Transfection with miR-34a mimic reduced lipid droplet formation during adipogenesis, while miR-34a inhibitor increased lipid droplet accumulation. Transfection with miR-34a mimic also reduced the mRNA and protein expression of ACSL4 and lipogenesis genes, including PPAR?, aP2, and SREBP-1C, but increased the expression of steatolysis genes such as ATGL and Sirt1. In contrast, the miR-34a inhibitor had the opposite effect on gene expression. Further, knockdown of ACSL4 decreased lipid droplet accumulation. CONCLUSIONS:Our results support the hypothesis that miR-34a regulates intramuscular fat deposition in porcine adipocytes by targeting ACSL4.
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