• Biomolecules & Therapeutics
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• 제29권2호
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• pp.211-219
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• 2021

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

• International Journal of Stem Cells
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• 제15권3호
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• pp.324-333
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• 2022

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid-associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and β-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of β-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and β-catenin, and inhibition of miR-29a-3p promoted translocation of β-catenin to the nucleus. Conclusions: MiR-29a-3p can modulate FOXO3 expression and Wnt/β-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권3호
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• pp.1075-1079
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• 2014

MicroRNA expression is a research focus in studies of tumors. This article concentrates attention on potential links between tumors caused by mouse mammary tumor virus (MMTV) and human breast cancer, in order to provide theoretical basis for using mouse model to search for miRNA effects mediated by Wnt/beta-catenin signaling in human breast cancer. By analyzing interactions between miRNAs and the Wnt/beta-catenin signaling pathway in breast cancer, we hope to casts light on more biological functions of miRNAs in the process of tumor formation and growth and to explore their potential value in cancer diagnosis, prognosis and treatment. Our endeavor aimed at providing theoretical basis for finding safer, more effective methods for treatment of human breast cancer at the miRNA molecular level.

• The Korean Journal of Physiology and Pharmacology
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• 제22권1호
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• pp.53-61
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• 2018

Ethyl linoleate is an unsaturated fatty acid used in many cosmetics for its various attributes, such as antibacterial and anti-inflammatory properties and clinically proven to be an effective anti-acne agent. In this study, we investigated the effect of ethyl linoleate on the melanogenesis and the mechanism underlying its action on melanogenesis in B16F10 murine melanoma cells. Our results revealed that ethyl linoleate significantly inhibited melanin content and intracellular tyrosinase activity in ${\alpha}$-MSH-induced B16F10 cells, but it did not directly inhibit activity of mushroom tyrosinase. Ethyl linoleate inhibited the expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase related protein 1 (TRP1) in governing melanin pigment synthesis. We observed that ethyl linoleate inhibited phosphorylation of Akt and glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$) and reduced the level of ${\beta}-catenin$, suggesting that ethyl linoleate inhibits melanogenesis through $Akt/GSK3{\beta}/{\beta}-catenin$ signal pathway. Therefore, we propose that ethyl linoleate may be useful as a safe whitening agent in cosmetic and a potential therapeutic agent for reducing skin hyperpigmentation in clinics.

• Molecules and Cells
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• 제43권2호
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• pp.188-197
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• 2020

Cells are designed to be sensitive to a myriad of external cues so they can fulfil their individual destiny as part of the greater whole. A number of well-characterised signalling pathways dictate the cell's response to the external environment and incoming messages. In healthy, well-ordered homeostatic systems these signals are tightly controlled and kept in balance. However, given their powerful control over cell fate, these pathways, and the transcriptional machinery they orchestrate, are frequently hijacked during the development of neoplastic disease. A prime example is the Wnt signalling pathway that can be modulated by a variety of ligands and inhibitors, ultimately exerting its effects through the β-catenin transcription factor and its downstream target genes. Here we focus on the interplay between the three-member family of RUNX transcription factors with the Wnt pathway and how together they can influence cell behaviour and contribute to cancer development. In a recurring theme with other signalling systems, the RUNX genes and the Wnt pathway appear to operate within a series of feedback loops. RUNX genes are capable of directly and indirectly regulating different elements of the Wnt pathway to either strengthen or inhibit the signal. Equally, β-catenin and its transcriptional co-factors can control RUNX gene expression and together they can collaborate to regulate a large number of third party co-target genes.

• Biomolecules & Therapeutics
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• 제29권6호
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• pp.643-649
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• 2021

Literature has revealed that the delta opioid receptor (DOR) exhibited diverse pharmacological effects on neuron and skin. In the present study, we have investigated whether the activation of DOR has hair-growth promotion effects. Compared with other opioid receptor, DOR was highly expressed in epidermal component of hair follicle in human and rodents. The expression of DOR was high in the anagen phase, but it was low in the catagen and telogen phases during mouse hair cycle. Topical application of UFP-512, a specific DOR agonist, significantly accelerated the induction of the anagen in C₃H mice. Topical application of UFP-512 also increased the hair length in hair organ cultures and promoted the proliferation and the migration of outer root sheath (ORS) cells. Similarly, pharmacological inhibition of DOR by naltrindole significantly inhibited the anagen transition process and decreased hair length in hair organ cultures. Thus, we further examined whether Wnt/β-catenin pathway was related to the effects of DOR on hair growth. We found that Wnt/β-catenin pathway was activated by UFP-512 and siRNA for β-catenin attenuated the UFP-512 induced proliferation and migration of ORS cells. Collectively, result established that DOR was involved in hair cycle regulation, and that DOR agonists such as UFP-512 should be developed for novel hair-loss treatment.

• BMB Reports
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• 제57권4호
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• pp.194-199
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• 2024

Overexpression of mitofusin-2 (MFN2), a mitochondrial fusion protein, is frequently associated with poor prognosis in cervical cancer patients. Here, I aimed to investigate the involvement of MFN2 in cervical cancer progression and determine the effect of MFN2 on prognosis in cervical cancer patients. After generating MFN2-knockdown SiHa cells derived from squamous cell carcinoma, I investigated the effect of MFN2 on SiHa cell proliferation using the Cell Counting Kit-8 assay and determined the mRNA levels of proliferation markers. Colony-forming ability and tumorigenesis were evaluated using a colony-formation assay and tumor xenograft mouse models. The migratory and invasive abilities associated with MFN2 were measured using wound-healing and invasion assays. Wnt/β-catenin-mediated epithelial-mesenchymal transition (EMT) markers related to MFN2 were assessed through quantitative RT-PCR. MFN2-knockdown SiHa cells exhibited reduced proliferation, colony formation, migration, invasion, and tumor formation in vivo. The motility of SiHa cells with MFN2 knockdown was reduced through Wnt/β-catenin-mediated EMT inhibition. MFN2 promoted cancer progression and tumorigenesis in SiHa cells. Overall, MFN2 could serve as a therapeutic target and a novel biomarker for cervical cancer.

• 생약학회지
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• 제44권4호
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• pp.384-390
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• 2013

This study was conducted to evaluate the effect of wheat bran on the promotion of hair growth. When rat vibrissa follicles were treated with n-hexane fraction of wheat bran, the hair-fiber lengths of the vibrissa follicles significantly increased. Moreover, n-hexane fraction of wheat bran was found to significantly induce the telogen-anagen transition in C57BL/6 mice. The fraction increased the proliferation of immortalized vibrissa dermal papilla cells (DPCs) in a dose dependent manner. To elucidate the molecular mechanisms in relation to proliferation of DPCs by the fraction of wheat bran, we examined the expression of cell cycle proteins and wnt/${\beta}$-catenin signaling components. Western blot analysis revealed that the proliferation of DPC by n-hexane fraction of wheat bran was accompanied by increased the level of cyclin D1, cyclin E, phospho-CDK2 and phospho-pRB. In addition, the fraction of wheat bran increased the level of phospho(ser552)-${\beta}$-catenin, phospho(ser675)-${\beta}$-catenin and phospho(ser9)-GSK$3{\beta}$. These results suggest that the hair growing potential of wheat bran mediated by proliferation of DPCs via the regulation of cell cycle proteins and Wnt/${\beta}$-catenin signaling.

• Asian Pacific Journal of Cancer Prevention
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• 제15권18호
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• pp.7617-7623
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• 2014

Objective: The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. Methods: The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implanted into nude mice for in vivo analysis, and cerulenin was used as a FASN inhibitor. RT-PCR, real-time quantitative PCR and Western blot were employed to detect the expression of FASN, TNFR-1, TNFR-2, Wnt-1, ${\beta}$-catenin and cytC at the RNA and protein levels. Results: Compared with MCF-7, TNFR-1 expression in MCF-7-MEK5 was slightly changed, TNFR-2 was decreased, and FASN, Wnt-1, ${\beta}$-catenin and cytC were increased. The expression of Wnt-1 and ${\beta}$-catenin in MCF-7-MEK5 decreased after cerulenin treatment, whereas cytC expression increased. Conclusions: The important function of FASN in the drug tolerance of breast cancer may be due to the following mechanisms: FASN downregulated TNFR-2 expression through lipid rafts to make the cells less sensitive to TNF-${\alpha}$, and simultaneously activated the Wnt-$1/{\beta}$-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.

• 생약학회지
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• 제47권2호
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• pp.143-149
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• 2016

Grateloupia elliptica has been reported to have the proliferation effect of dermal papilla cells (DPCs), which play important roles in the regulation of hair cycle. In the present study, we examined in vitro and in vivo hair growth-promoting effect of Grateloupia elliptica. When isolated rat vibrissa follicles were treated with extract of G. elliptica, the hair-fiber lengths of the vibrissa follicles significantly increased. Furthermore, the G. elliptica extract accelerated the telogen-angen transition in C57BL/6 mice. To investigate the molecular mechanisms of the G. elliptica extract on the proliferation of DPCs, we examined the activation of $wnt/{\beta}$-catenin signaling which is known to regulate hair follicle development, differentiation and hair growth. The G. elliptica extract activated $wnt/{\beta}$-catenin signaling via the increase of ${\beta}$-catenin and phospho-$GSK3{\beta}$. In addition, the G. elliptica extract increased the level of cyclin E and CDK2, while the level of $p27^{kip1}$ was decreased. These results suggest that the the G. elliptica extract may induce hair growth by proliferation of DPCs via cell-cycle progression and the activation of $Wnt/{\beta}$-catenin signaling.