CELL CYCLE
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2021
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IF 4.534
Jun Zhu,Qiwei Fu,Jiahua Shao,Jinhui Peng,Qirong Qian,Yiqin Zhou,Yi Chen
This study explored the role of MEG3 in the cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effects of over-expression and knockdown of MEG3 on cell viability, cell differentiation, and the expressions of MEG3, miR-129-5p, COL2, chondrocyte differentiation-related genes (sry-type high-mobility-group box 9 (SOX9), SOX5, Aggrecan, silent information regulator 1 (SIRT1), and Cartilage oligomeric matrix protein (COMP)). The targeting relationship between MEG3 and miR-129-5p and the target gene of miR-129-5p was confirmed through Starbase, TargetScan and luciferase experiments. Finally, a series of rescue experiments were conducted to study the regulatory effects of MEG3 and miR-129-5p. BMSCs were identified as CD29+ and CD44+ positive, and their differentiation was time-dependent. As BMSCs differentiated, MEG3 expression was up-regulated, but miR-129-5p was down-regulated. Over-expressed MEG3 promoted the viability and differentiation of BMSCs, up-regulated the expressions of COL2 and chondrocyte differentiation-related genes, and inhibited miR-129-5p. Runt-related transcription factor 1 (RUNX1) was negatively regulated as a target gene of miR-129-5p. Results of rescue experiments showed that the inhibitory effect of miR-129-5p mimic on BMSCs could be partially reversed by MEG3. Over-expression of MEG3 regulated the miR-129-5p/RUNX1 axis to promote the differentiation of BMSCs into chondrocytes. This study provides a reliable basis for the application of lncRNA in articular cartilage injury.
研究领域:
干细胞生物学
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分子生物学
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再生医学
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骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PATHOLOGY RESEARCH AND PRACTICE
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2022
·
IF 3.309
Hong Zhang,Qi Zhou,Jue Jiang
Background Previous data have shown that circular RNA (circRNA) is a key regulator in papillary thyroid cancer (PTC). However, the role and the detailed mechanism of circ_0027446 in PTC progression have not been reported. Methods Circ_0027446, miR-129–5p, claudin 1 (CLDN1), C-myc and MMP2 expression were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot or immunohistochemistry (IHC) assay. Cell viability was evaluated by cell counting kit-8 (CCK-8) assay. Cell proliferation was investigated by 5-Ethynyl-2′-deoxyuridine (EdU) assay and cell colony formation assay. Cell apoptosis , invasion and migration were assessed by flow cytometry analysis, transwell assay and wound-healing assay, respectively. Dual-luciferase reporter assay was conducted to identify the associations among circ_0027446, miR-129–5p and CLDN1. The effect of circ_0027446 on PTC cell malignancy in vivo was revealed by a xenograft mouse model assay. Results Circ_0027446 and CLDN1 expression were significantly upregulated, while miR-129–5p expression was downregulated in PTC tissues and cells. High circ_0027446 expression was closely associated with the poor prognosis of PTC patients . Circ_0027446 depletion inhibited PTC cell proliferation, migration and invasion but increased cell apoptosis. In addition, circ_0027446 acted as a miR-129–5p sponge, and miR-129–5p bound to CLDN1. Moreover, miR-129–5p inhibitors attenuated circ_0027446 depletion-induced effects in PTC cells. CLDN1 also participated in the regulation of miR-129–5p in PTC cell tumor properties. Importantly, circ_0027446 mediated CLDN1 expression by interacting with miR-129–5p. In vivo data showed that the decreased expression of circ_0027446 led to delayed tumor formation. Conclusion Circ_0027446 contributed to PTC cell tumor properties by regulating the miR-129–5p/CLDN1 pathway, showing circ_0027446 might be a therapeutic target in PTC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL GENETICS
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2023
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IF 2.4
Yuan Hang,Yu Peng,Wan Zi-Ang,Chen Bing-Chen,Tu Shi-Liang
We previously reported that long non-coding RNA (lncRNA) RPLP0P2 is involved in the progression of colorectal cancer (CRC); however, its molecular mechanisms in CRC remain unclear. In this study, we observed that RPLP0P2 was upregulated in CRC tissues and cell lines. Cell viability was measured using the MTT and colony formation assays. Migration and invasion capabilities were monitored by wound healing, transwell, and immunofluorescence assays. The results showed that RPLP0P2 downregulation inhibited cell viability, migration, and invasion capabilities of CRC cells, accompanied by decreased PCNA, N-cadherin, and Vimentin, and increased E-cadherin expression. Using the DIANA online database, miR-129-5p was identified as a downstream target of RPLP0P2. In fact, RPLP0P2 colocalized with miR-129-5p, acting as a miR-129-5p sponge. MiR-129-5p-inhibition almost abrogated the anti-tumor effects induced by RPLP0P2 inhibition in CRC cells. Zinc finger and BTB domain-containing 20 (ZBTB20) was identified as a potential downstream target of miR-129-5p in CRC cells. ZBTB20 overexpression prevented miR-129-5p mimic-mediated anti-tumor effects in CRC cells. A tumor xenograft assay was performed to monitor the role of RPLP0P2 in tumor growth. Of note, in tumor-bearing mice, RPLP0P2-silencing inhibited tumor growth, followed by increased miR-129-5p and decreased ZBTB20 expression. Our results suggest that lncRNA RPLP0P2 functions as an oncogene that promotes CRC cell proliferation and invasion via regulating the miR-129-5p/ZBTB20 axis, thus, it may serve as a candidate target for CRC interventional therapies.
研究领域:
肿瘤学
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分子生物学
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癌症研究
✓ 已验证
DOI
PubMed
高影响因子
EXPERIMENTAL BRAIN RESEARCH
·
2021
·Vol. 239
·期 11
·3359-3370
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IF 1.972
Chang Jie,Zhang Yanhong,Shen Nianhong,Zhou Jingquan,Zhang Huan
Depression is a complex etiological disease with limited effective treatments. Previous studies have indicated the involvement of miRNAs in the pathophysiology of mood disorders. In this study, we focused on the role and mechanisms of miR-129-5p in depression by successfully constructing mice models of depressive-like behavior via chronic unpredictable mild stress (CUMS) exposure. Herein, miR-129-5p expression was decreased in the hippocampus of CUMS mice model. Upregulation of miR-129-5p reduced depressive-like behaviors of CUMS mice, as revealed in sucrose preference test, novelty suppressed feeding test, forced swim test, tail suspension test, social interaction test. MiR-129-5p upregulation decreased the concentrations and protein levels of proinflammatory cytokines (IL-6, IL-1β and TNF-α), indicating the inhibitory role of miR-129-5p in inflammation. Furthermore, miR-129-5p was identified to target MAPK1. MAPK1 was negatively regulated by miR-129-5p, and silencing of MAPK1 attenuated depressive-like behaviors in CUMS mice. Moreover, MAPK1 downregulation decreased inflammation in the hippocampus of CUMS mice. Upregulation of MAPK1 reversed the suppressive effects of miR-129-5p upregulation on depressive-like behaviors and inflammation in CUMS mice. In conclusion, the current study identified that miR-129-5p reduces depressive-like behaviors and suppresses inflammation by targeting MAPK1 in CUMS mice, offering a novel molecular interpretation for depression prevention.
研究领域:
神经科学
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分子生物学
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精神病学
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DOI
PubMed
高影响因子
Cell Death Discovery
·
2022
·Vol. 8
·期 1
·1-11
·
IF 7.109
Zhang Fangbin,Guo Changqing,Cao Xinguang,Yan Yan,Zhang Jinping,Lv Shuai
Cancer cell-derived extracellular vesicles (EVs) have extensive application in the formation of their environment, including metastasis. This study explored the ability of gastric cancer (GC) cell-derived EVs-mediated microRNA-129-5p/E2F transcription factor 7/mitogen-activated protein kinase/extracellular regulated protein kinase (miR-129-5p/E2F7/MAPK/ERK) axis to affect the peritoneal metastasis of GC by delivering lncRNA small nucleolar RNA host gene 12 (SNHG12). EV-derived lncRNA and SNHG12/miR-129-5p/E2F7 network were determined by bioinformatics analysis. The regulatory relationship among SNHG12, miR-129-5p, and E2F7 was verified using a combination of dual-luciferase reporter gene, RNA immunoprecipitation, and RNA pull-down assays. The SNHG12, miR-129-5p, and E2F7 expression was measured by RT-qPCR. After GC cell-derived EVs were isolated and co-cultured with human peritoneal mesothelial cells (HPMCs), the uptake of EVs by HPMCs was observed under laser scanning confocal microscopy. Cell viability and apoptosis were examined using cell counting kit-8 and flow cytometry, respectively. Western blot analysis was performed to measure the mesothelial–mesenchymal transition (MMT)-related protein expression. The pathological and morphological characteristics of metastatic tumors in nude mice were observed by hematoxylin–eosin staining. A high SNHG12 expression was correlated with the poor prognosis of patients with GC. GC-derived EVs led to increased HPMC apoptosis and MMT by transferring SNHG12, whereas the knockdown of SNHG12 annulled the aforementioned results. SNHG12 sponged miR-129-5p to boost E2F7 expression and activate the MAPK/ERK signaling, thus inducing HPMC apoptosis and MMT. In vivo experiments further verified that EVs derived from GC cells promoted peritoneal metastasis in nude mice. GC cell-derived EVs elevated the E2F7 expression and activated the MAPK/ERK signaling to promote peritoneal metastasis through the delivery of SNHG12.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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