BMC GASTROENTEROLOGY
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2023
·Vol. 23
·期 1
·1-10
·
IF 2.4
Xiang Ping,Ge Tingrui,Zhou Jingyi,Zhang Yonggang
Background Increasing research indicates that circular RNAs (circRNAs) play critical roles in the development of ulcerative colitis (UC). This study aimed to determine the role of circRNA CCND1 in UC bio-progression, which has been shown to be downregulated in UC tissues. Methods Reverse transcription quantitative polymerase chain reaction was used to determine the levels of circRNA CCND1 , miR-142-5p, and nuclear receptor coactivator-3 ( NCOA3 ) in UC tissues and in lipopolysaccharide (LPS)-induced Caco-2 cells. Target sites of circRNA CCND1 and miR-142-5p were predicted using StarBase, and TargetScan to forecast potential linkage points of NCOA3 and miR-142-5p, which were confirmed by a double luciferase reporter-gene assay. Cell Counting Kit 8 and flow cytometry assays were performed to assess Caco-2 cell viability and apoptosis. TNF-α, IL-1β, IL-6, and IL-8 were detected using Enzyme-Linked Immunosorbent Assay kits. Results CircRNA CCND1 was downregulated in UC clinical samples and LPS-induced Caco-2 cells. In addition, circRNA CCND1 overexpression suppressed LPS-induced apoptosis and inflammatory responses in Caco-2 cells. Dual-luciferase reporter-gene assays showed that miR-142-5p could be linked to circRNA CCND1 . Moreover, miR-142-5p was found to be highly expressed in UC, and its silencing inhibited LPS-stimulated Caco-2 cell apoptosis and inflammatory responses. Importantly, NCOA3 was found downstream of miR-142-5p. Overexpression of miR-142-5p reversed the inhibitory effect of circRNA CCND1 -plasmid on LPS-stimulated Caco-2 cells, and the effects of miR-142-5p inhibitor were reversed by si- NCOA3 . Conclusion CircRNA CCND1 is involved in UC development by dampening miR-142-5p function, and may represent a novel approach for treating UC patients.
研究领域:
分子生物学
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胃肠病学
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免疫学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR REPRODUCTION AND DEVELOPMENT
·
2015
·Vol. 82
·期 4
·305-314
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IF 2.527
Wei-Rong Yang,Yong Wang,Yi Wang,Jiao-Jiao Zhang,Jia-Hua Zhang,Cheng Lu,Xian-Zhong Wang
SUMMARY Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital role in the cell cycle. Within the testis, estrogen also plays an important role in Sertoli cell proliferation, although it is not clear how. The present study asked if mTOR is involved in 17β-estradiol-dependent Sertoli cell proliferation. We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent effects toward the activation of mTOR signaling, and if this signaling regulates the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17β-estradiol for 15–90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. U0126 (5 μM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 μM), a selective inhibitor of AKT, both significantly reduced 17β-estradiol-induced phosphorylation of mTOR. Rapamycin suppressed 17β-estradiol-induced Sertoli cell proliferation, appearing to act by reducing the abundance of SKP2 , CCND1 , and CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 17β-estradiol enhances Sertoli cell proliferation via mTOR activation, which involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 and CCNE1 , and inhibits SKP2 protein degradation by increasing EMI1 abundance. Mol. Reprod. Dev. 82: 305–314, 2015. © 2015 Wiley Periodicals, Inc .
研究领域:
生殖生物学
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细胞信号传导
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Aging-US
·
2020
·
IF 4.831
Min Nie,Yadong Wang,Zenong Yu,Xinyu Li,Yexuan Deng,Ying Wang,Dongjun Yang,Qixiang Li,Xiangwei Zeng,Junyi Ju,Ming Liu,Quan Zhao
Aurora kinase B (AURKB) triggers the phosphorylation of serine 10 on histone H3 (H3S10ph), which is important for chromosome condensation and cytokinesis during mitosis in mammals. However, how exactly AURKB controls cell cycle and contributes to tumorigenesis as an oncoprotein under pathological conditions remains largely unknown. Here, we report that AURKB promotes gastric cancer cell proliferation in vitro and in vivo . Silencing AURKB expression inhibits gastric cell proliferation and arrests the cell cycle in G 2 /M phase. We demonstrate that cyclin D1 (CCND1) is a direct downstream target of AURKB that plays a key role in gastric cancer cell proliferation. AURKB is able to activate the expression of CCND1 through mediating H3S10ph in the promoter of the CCND1 gene. Furthermore, we show that AZD1152, a specific inhibitor of AURKB, can suppress the expression of CCND1 in the gastric cancer cells and inhibit cell proliferation in vitro and in vivo . Importantly, we found that high AURKB and CCND1 expression levels are correlated with shorter overall survival of gastric cancer patients. This study demonstrates that AURKB promotes gastric tumorigenesis potentially through epigenetically activating CCND1 expression, suggesting AURKB as a promising therapeutic target in gastric cancer.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Communications Biology
·
2025
·Vol. 8
·期 1
·1-15
·
IF 5.1
Wang Xue,Yan Guangqi,Li Hao,Wang Chunyu,Kang Ye,Wang Shengli,Liu Wei,Lin Lin,Zou Renlong,Zeng Kai,Wang Manlin,Luan Ruina,Zhou Baosheng,Bai Yu,Yang Dongjun,Ning Bolin,Sun Ge,Zhao Yue
Oral squamous cell carcinoma (OSCC) progresses from epithelial cell proliferation to malignancy. Given the higher proportion of male patients compared to female patients, the androgen signaling pathway is believed to play a significant role in promoting epithelial cell proliferation. However, the underlying molecular mechanisms remain unclear. Here, we identified RBAP48 as a novel androgen receptor (AR) co-activator in OSCC cells. Our results show that RBAP48 was highly expressed in OSCC tumor tissues from patients with a poor prognosis. Further, RBAP48 knockdown decreased genome-wide oncogene transcription. RBAP48 and AR interacted to activate CCND1 and RAB31 transcription, and upregulated RELA and CCNE1 mRNA expression through an AR-independent pathway. Additionally, RBAP48 promoted OSCC cell proliferation and was involved in the cellular response to drugs and external compounds in vitro, ultimately driving cancer progression. Our results indicate that RBAP48 is a novel oncogene and a promising target for predicting and treating OSCC progression.
研究领域:
肿瘤学
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分子生物学
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医学遗传学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-12
·
IF 16.6
Chen Zhigang,Zhang Yi,Li Wenlu,Gao Chenyi,Huang Fengbo,Cheng Lu,Jin Menglei,Xu Xiaoming,Huang Jian
Fibroadenomas (FAs) are the most common breast tumors in women. No pharmacological agents are currently approved for FA intervention owing to its unclear mechanisms and a shortage of reproducible human models. Here, using single-cell RNA sequencing of human FAs and normal breast tissues, we observe distinct cellular composition and epithelial structural changes in FAs. Interestingly, epithelial cells exhibit hormone-responsive functional signatures and synchronous activation of estrogen-sensitive and hormone-resistant mechanisms ( ERBB2 , BCL2 and CCND1 pathways). We develop a human expandable FA organoid system and observe that most organoids seem to be resistant to tamoxifen. Individualized combinations of tamoxifen with ERBB2, BCL2 or CCND1 inhibitors could significantly suppress the viability of tamoxifen-resistant organoids. Thus, our study presents an overview of human FA at single-cell resolution that outlines the structural and functional differences between FA and normal breast epithelium and, in particular, provides a potential therapeutic strategy for breast FAs.
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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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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