miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration

Teng, Zhaowei; Xie, Xue-guan; Zhu, Yun; Liu, Jianping; Hu, Xingbo; Qiang, Na; Zhang, Xiongwen; Wei, Guojun; Xu, Shangcheng; Liu, Yugang; Chen, Xian

doi:10.1155/2018/3274641

Cited by 15 publications

(11 citation statements)

References 25 publications

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“…miRNAs also regulate the differentiation of mesenchymal stem cells and osteoblasts (19,20). During the processes of bone differentiation and regeneration, abnormal miRNA expression is closely associated with OP (21,22). For example, the miR-34c-induced silencing of MC3T3-E1 reduces the inhibitory effect of vaspin on osteoblast differentiation (23); furthermore, miRNA (miR)-433-3p can regulate osteoblastic differentiation by targeting Dickkopf-1 ( DKK1 ) (24).…”

Section: Introductionmentioning

confidence: 99%

miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1

Tang

Huang

et al. 2019

Mol Med Report

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Osteoporosis (OP) seriously affects the health and quality of life of elderly individuals and postmenopausal women, and the need to identify drugs that can prevent or treat OP remains urgent. Recently, several miRNAs have been reported to be involved in the differentiation of mesenchymal stem cells and osteoblasts; however, the role of miRNA (miR)-144 in regulating OP remains to be elucidated. In the present study, the expression levels of miR-144, secreted frizzled-related protein 1 (Sfrp1) and TNF-α in clinical samples were detected by the reverse transcription-quantitative polymerase chain reaction analysis and ELISA, respectively. 5-Ethynyl-2′-deoxyuridine staining, Hoechst 33258 staining, flow cytometry, a clone formation assay and Alizarin red staining were used to assess the effects of miR-144 combined with or without Sfrp1 small interfering RNA on the proliferation, apoptosis and osteoblastic differentiation of primary mesenchymal stem cells isolated from rats. Western blot assays were performed to assess the relevant mechanisms, and a dual luciferase reporter assay was used to detect the interaction between miR-144 and Sfrp1. The results showed that the levels of miR-144, Sfrp1 and TNF-α in clinical serum samples obtained from patients with postmenopausal OP were higher than those in serum samples obtained from postmenopausal women with normal bone density. There was a significant positive correlation between miR-144 and Sfrp1. Functional experiments demonstrated that miR-144 promoted proliferation, inhibited apoptosis and induced the osteoblastic differentiation of bone marrow-derived mesenchymal stem cells by targeting Sfrp1 . It was also shown that miR-144 may help regulate OP by activating the Wnt/β-catenin pathway. These data suggest miR-144 as a novel target for preventing and treating OP.

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Section: Introductionmentioning

confidence: 99%

miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1

Tang

Huang

et al. 2019

Mol Med Report

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“…As a postmenopausal osteoporosis disease model Teng et al . [ 19 ] analyzed a total miRNA expression analysis in bone marrow derived mesenchymal stem cells of mice with oophorectomy. In all miRNAs , the expression level of miR-142-5p increased the most compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

“…VCAM1 was decreased in HEK293T cells, as revealed by luciferase assay. VCAM-1 has an important role in cell-cell recognition, inflammation, development of various organs and formation of immune responses and is also involved in the activation and migration of immune cells [ 19 ]. The increased expression of miR-142-5p and reduced expression of VCAM-1 demonstrated in the osteoporosis model by Teng et al .…”

Section: Discussionmentioning

confidence: 99%

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The expression levels of microRNAs associated with T and B cell differentiation/stimulation in ankylosing spondylitis

Turkyilmaz

Ata

Akbaş

et al. 2020

Balkan Journal of Medical Genetics

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Spondyloarthropathies (SpAs), are a group of chronic inflammatory diseases with a number of genetic, physiopathological, clinical and radiological features. Ankylosing spondylitis (AS) is the most common type of spondylo-arthropathies, and >90.0% of patients with ankylosing spondylitis are human leukocyte antigen-B27 (HLA-B2 7)-positive. In recent years, non-HLA genetic factors have been reported to have an effect on ankylosing spondylitis. MicroRNAs (miRNAs), are endogenous non coding RNA molecules containing 18-23 nucleotides that play a role in the post-transcriptional regulation of gene expression. In this study, we aimed to determine the expression levels of miRNAs associated with T- and B-cell differentiation/stimulation in peripheral blood mononuclear cells and their relationship with the etiology of the AS in patients and healthy controls. In a molecular study, peripheral blood mononuclear cell isolation, and total RNA isolation were performed first. In the second step, cDNA synthesis and quantitative real-time PCR (qPCR) expression analysis were completed. Ultimately, in the patient and control group, the expression levels of miR-142-5p and miR-143 were found to be significantly different (p <0.05). According to current knowledge, miR-142-5p andmiR-143 expressions were found to be important for those diseases that share similar etiology with AS. We suggest that miR-142-5p and miR-143 may play a role in the pathogenesis, especially miR- 142-5p may be a potential biomarker and a target molecule for the treatment.

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“…More importantly, our results also provide a potential link between miR-142-5p and the self-renewal ability of ESCC cells where exogenous miR-142-5p led to a decreased ability to generate tumor spheres in both OE21 and OE33 cells. A recent study indicated that miR-142-5p functioned to suppress cell migration by targeting VCAM-1 in bone marrow-derived mesenchymal stem cells [40]. Trisaal et al showed that loss-of-function the in miR-142 gene resulted in the increase in HOXA gene (a key gene for maintaining stemness in hematopoietic stem cells) and promoted leukemogenesis [41].…”

Section: Discussionmentioning

confidence: 99%

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

Huang

Hsu

et al. 2019

Cells

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Elevated activity of sterol regulatory element-binding protein 1 (SREBP1) has been implicated in the tumorigenesis of different cancer types. However, the functional roles of SREBP1 in esophageal cancer are not well appreciated. Here, we aimed to investigate the therapeutic potential of SREBP1 and associated signaling in esophageal cancer. Our initial bioinformatics analyses showed that SREBP1 expression was overexpressed in esophageal tumors and correlated with a significantly lower overall survival rate in patients. Additionally, tumor suppressor miR-142-5p was predicted to target SREBP1/ZEB1 and a lower miR-142-5p was correlated with poor prognosis. We then performed in vitro experiments and showed that overexpressing SREBP1 in OE33 cell line led to increased abilities of colony formation, migration, and invasion; the opposite was observed in SREBP1-silenced OE21cells and SREBP1-silencing was accompanied by the reduced mesenchymal markers, including vimentin (Vim) and ZEB1, while E-cadherin and tumor suppressor miR-142-5p were increased. Subsequently, we first demonstrated that both SREBP1 and ZEB1 were potential targets of miR-142-5p, followed by the examination of the regulatory circuit of miR-142-5p and SREBP1/ZEB1. We observed that increased miR-142-5p level led to the reduced tumorigenic properties, such as migration and tumor sphere formation, and both observations were accompanied by the reduction of ZEB1 and SREBP1, and increase of E-cadherin. We then explored the potential therapeutic agent targeting SREBP1-associated signaling by testing fatostatin (4-hydroxytamoxifen, an active metabolite of tamoxifen). We found that fatostatin suppressed the cell viability of OE21 and OE33 cells and tumor spheres. Interestingly, fatostatin treatment reduced CD133+ population in both OE21 and OE33 cells in concert of increased miR-142-5p level. Finally, we evaluated the efficacy of fatostatin using a xenograft mouse model. Mice treated with fatostatin showed a significantly lower tumor burden and better survival rate as compared to their control counterparts. The treatment of fatostatin resulted in the reduced staining of SREBP1, ZEB1, and Vim, while E-cadherin and miR-142-5p were increased. In summary, we showed that increased SREBP1 and reduced miR-142-5p were associated with increased tumorigenic properties of esophageal cancer cells and poor prognosis. Cells 2020, 9, 7 2 of 15Preclinical tests showed that suppression of SREBP1 using fatostatin led to the reduced malignant phenotype of esophageal cancer via the reduction of EMT markers and increased tumor suppressor, miR-142-5p. Further investigation is warranted for the clinical use of fatostatin for the treatment of esophageal malignancy.

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miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration

Cited by 15 publications

References 25 publications

miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1

miR‑144 promotes the proliferation and differentiation of bone mesenchymal stem cells by downregulating the expression of SFRP1

The expression levels of microRNAs associated with T and B cell differentiation/stimulation in ankylosing spondylitis

Disruption of Cancer Metabolic SREBP1/miR-142-5p Suppresses Epithelial–Mesenchymal Transition and Stemness in Esophageal Carcinoma

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