Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis

Sheng, Yanrui; Ding, Shijia; Chen, Ke; Chen, Juan; Wang, Sen; Zou, Chengcheng; Zhang, Jingnan; Cao, Yiyi; Huang, Aiping; Tang, Hua

doi:10.1139/bcb-2013-0128

Cited by 31 publications

(17 citation statements)

References 35 publications

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“…RAP1B is a member of the Ras superfamily of GTPases (10), and altered RAP1B expression is associated with human carcinogenesis (7,11,13,14,16,18). In the present study, we first analyzed RAP1B and HIF-1α expression in GC tissue specimens and found that RAP1B was highly expressed in GC tissues and that its expression was associated with malignant behaviors and a poor overall survival of GC patients.…”

Section: Discussionmentioning

confidence: 85%

“…RAP1B also functions as a key suppressor of neutrophil migration and lung inflammation (12). Other studies have shown that altered RAP1B expression occurs in several types of human cancer and that RAP1B promotes cancer growth, invasion and metastasis (7,11,(13)(14)(15)(16)(17)(18). Specifically, RAP1B expression is upregulated in late-stage ovarian tumors and inhibition of RAP1B expression suppressed tumor cell migration/invasion in vitro and also suppressed the abdominal metastasis of an orthotopic xenograft mouse model (11).…”

Section: Expression Of Rap1b Is Associated With Poor Prognosis and Prmentioning

confidence: 99%

“…Towards this end, our research focuses on Ras-related protein Rap1, which is a member of the Ras superfamily of GTPases. The function of these GTPases in cells is to shuttle between inactive GDP-and active GTP-bound states, thus regulating multiple cellular processes including cell adhesion, migration, polarity, differentiation, growth and angiogenesis (7,8). RAP1B is an isoform of Rap1 and possesses different functions in different cells (9,10).…”

Section: Introductionmentioning

confidence: 99%

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Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer

Yang

Yan

et al. 2015

Oncology Reports

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Metastasis is the major cause of death among gastric cancer (GC) patients, and altered expression of Ras-related protein RAP1B is associated with cancer development. The present study assessed RAP1B expression ex vivo and the effect of hypoxia‑induced RAP1B overexpression on the promotion of the metastatic potential of GC cells in vitro. Immunohistochemistry was used to detect the expression of RAP1B and hypoxia‑inducible factor-1α (HIF-1α) in 178 GC tissue specimens. GC cell lines were used to assess the effects of hypoxia and RAP1B knockdown with RAP1B small interfering RNA (siRNA). Tumor cell viability was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, invasion capacity was evaluated by a Transwell assay, and gene expression was determined by qRT-PCR and western blotting. The data showed that expression levels of RAP1B and HIF-1α proteins were high in the GC tissue specimens, and RAP1B expression was significantly associated with tumor-node-metastasis (TNM) stage and tumor size, while HIF-1α expression was significantly associated with TNM stage, Borrmann type and tumor differentiation. Moreover, RAP1B expression was associated with HIF-1α expression (r=0.547, P<0.001). The expression of RAP1B and HIF-1α proteins was associated with a shorter overall survival of patients according to the univariate analysis (log-rank test, P<0.01), and RAP1B expression and TNM stage were independent prognostic predictors in patients using a multivariate analysis (P<0.001). In vitro, hypoxia induced the invasion of GC cells and the expression of RAP1B and HIF-1α (P<0.05); whereas knockdown of RAP1B expression using siRNA inhibited the tumor cell invasion capacity even under hypoxic culture conditions (P<0.05). In conclusion, the protein expression of RAP1B and HIF-1α contributed to GC malignant behavior and poor prognosis. Future studies will evaluate whether targeting RAP1B expression can be used as a novel strategy to control GC or as a biomarker for prognosis prediction.

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Section: Discussionmentioning

confidence: 85%

Section: Expression Of Rap1b Is Associated With Poor Prognosis and Prmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer

Yang

Yan

et al. 2015

Oncology Reports

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“…Several lines of evidence have demonstrated that miR-101-3p is downregulated in various types of cancer, including hepatocellular carcinoma, non-small cell lung cancer and gastric cancer (19,26,27). In line with these studies, the downregulation of miR-101-3p was also identified in retinoblastoma, suggesting that miR-101-3p may serve an important role in the development and progression of this disease.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

Chen

et al. 2018

Exp Ther Med

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Retinoblastoma is the most frequent intraocular malignant tumor type to occur in childhood. MicroRNA (miR)-101-3p has been reported to function as a tumor suppressor in various types of cancer. However, the biological function and underlying mechanisms of miR-101-3p in retinoblastoma are largely unknown. In the present study, it was identified that miR-101-3p was downregulated in retinoblastoma. MTT and flow cytometry assays demonstrated that ectopic overexpression of miR-101-3p significantly inhibited cell viability and cell cycle progression in WERI-Rb-1 and Y79 cells. In vivo mouse experiments further confirmed the anti-proliferative role of miR-101-3p in retinoblastoma. Additionally, predictions with TargetScan software indicated that the 3′-untranslated regions of enhancer of zeste homolog 2 (EZH2) and histone deacetylase (HDAC9) mRNAs are targeted by miR-101-3p. Accordingly, a dual luciferase reporter gene assay demonstrated that miR-101-3p directly targeted EZH2 and HDAC9 to suppress the proliferation of retinoblastoma cells. Meanwhile, the restoration of EZH2 or HDAC9 expression countered the anti-proliferative effect of miR-101-3p on WERI-Rb-1 and Y79 cells. Collectively, these data highlight the role of miR-101-3p in the tumorigenesis of retinoblastoma, and indicate its suitability as a novel therapeutic target.

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“…Accumulating miRNAs have been delineated as critical regulators of T cells, macrophages, and synovial fibroblasts during the development of RA, such as miR-155 being a significant mediator for the innate immune responses contributing to autoimmune arthritis [14,15]. Multiple studies have indicated the tumor suppressor role of microRNA-101-3p (miR-101-3p) in a variety of malignancies, like hepatocellular carcinoma [16] and bladder cancer [17]. Specifically, miR-101-3p has been suggested to attenuate the cell viability, and metastatic potential of lung carcinoma cells by targeting and inhibiting the expression of enhancer of zeste homologue 2 (EZH2) [18].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2

Wei

Zhang

et al. 2020

Bioscience Reports

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Objective: Rheumatoid arthritis (RA) is the most frequently occurring inflammatory arthritis. The present study was performed to characterize the role of microRNA-101-3p (miR-101-3p) and prostaglandin-endoperoxide synthase 2 (PTGS2) in inflammation and biological activities of fibroblast-like synoviocytes (FLSs) in RA. Methods: Initially, miR-101-3p and PTGS2 expression in RA tissues of RA patients and RA rats was detected by qRT-PCR and Western blot analysis. Rat model of type II collagen-induced arthritis (CIA) was adopted to simulate RA, followed by injection of miR-101-3p mimics or siRNA against PTGS2. Next, the apoptosis in synovial tissue and the levels of tumor necrosis factor (TNF)-α, IL-1β and IL-6 were identified. Subsequently, FLSs in RA (RA-FLSs) were isolated, after which in vitro experiments were conducted to analyze cell proliferation, apoptosis, migration and invasion upon treatment of up-regulated miR-101-3p and silenced PTGS2. Furthermore, the relationship of miR-101-3p and PTGS2 was determined by bioinformatics prediction and luciferase activity assay. Results: We identified poorly expressed miR-101-3p and highly expressed PTGS2 in synovial tissues of RA patients and RA rats, which showed reduced synoviocyte apoptosis and enhanced inflammation. In response to miR-101-3p mimics and si-PTGS2, the RA-FLSs were observed with attenuated cell proliferation, migration and invasion, corresponding to promoted apoptosis. Down-regulation of PTGS2 could rescue the effect of inhibited miR-101-3p in synovial injury and phenotypic changes of FLS in RA rats. Notably, miR-101-3p was found to negatively regulate PTGS2. Conclusion: Taken together, miR-101-3p reduces the joint swelling and arthritis index in RA rats by down-regulating PTGS2, as evidenced by inhibited FLS proliferation and inflammation.

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Functional analysis of miR-101-3p and Rap1b involved in hepatitis B virus-related hepatocellular carcinoma pathogenesis

Cited by 31 publications

References 35 publications

Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer

Expression of RAP1B is associated with poor prognosis and promotes an aggressive phenotype in gastric cancer

MicroRNA‑101‑3p inhibits proliferation in retinoblastoma cells by targeting EZH2 and HDAC9

MicroRNA-101-3p inhibits fibroblast-like synoviocyte proliferation and inflammation in rheumatoid arthritis by targeting PTGS2

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