MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells

Zhang, Xiao; Hu, Shijie; Zhang, Xiang; Wang, Lei; Zhang, Xiaofang; Yan, Bo; Zhao, Jing; Yang, Angang; Zhang, Rui

doi:10.1016/j.bbrc.2013.12.095

Cited by 99 publications

(79 citation statements)

References 38 publications

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“…S2B), we selected nine downregulated genes with a cutoff value of <1.5, associated with cell-cycle progression and identified by both bioinformatic platforms (Table 1). In agreement with the role of TRAP1 in regulating cell-cycle progression, these genes are all responsible for the regulation of G 0 -G 1 and/or G 2 -M transitions (28)(29)(30)(31)(32)(33)(34)(35), with most of them activated by ERK signaling (36). To validate the microarray data, the expressions of eight of these genes were analyzed by quantitative PCR and immunoblot analyses in scramble/shTRAP1 HCT116 cells (Fig.…”

Section: Trap1 Regulates Braf Synthesis/ubiquitination At Translationmentioning

confidence: 59%

TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors

et al. 2014

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Human BRAF-driven tumors are aggressive malignancies with poor clinical outcome and lack of sensitivity to therapies. TRAP1 is a HSP90 molecular chaperone deregulated in human tumors and responsible for specific features of cancer cells, i.e., protection from apoptosis, drug resistance, metabolic regulation, and protein quality control/ubiquitination. The hypothesis that TRAP1 plays a regulatory function on the BRAF pathway, arising from the observation that BRAF levels are decreased upon TRAP1 interference, was tested in human breast and colorectal carcinoma in vitro and in vivo. This study shows that TRAP1 is involved in the regulation of BRAF synthesis/ubiquitination, without affecting its stability. Indeed, BRAF synthesis is facilitated in a TRAP1-rich background, whereas increased ubiquitination occurs upon disruption of the TRAP1 network that correlates with decreased protein levels. Remarkably, BRAF downstream pathway is modulated by TRAP1 regulatory activity: indeed, TRAP1 silencing induces (i) ERK phosphorylation attenuation, (ii) cell-cycle inhibition with cell accumulation in G 0 -G 1 and G 2 -M transitions, and (iii) extensive reprogramming of gene expression. Interestingly, a genome-wide profiling of TRAP1-knockdown cells identified cell growth and cell-cycle regulation as the most significant biofunctions controlled by the TRAP1 network. It is worth noting that TRAP1 regulation on BRAF is conserved in human colorectal carcinomas, with the two proteins being frequently coexpressed. Finally, the dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells. Therefore, this novel TRAP1 function represents an attractive therapeutic window to target dependency of BRAF-driven tumors on TRAP1 translational/quality control machinery. Cancer Res; 74(22); 6693-704. Ó2014 AACR.

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Section: Trap1 Regulates Braf Synthesis/ubiquitination At Translationmentioning

confidence: 59%

TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors

et al. 2014

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“…Zhou’ et al reported that miR-7 inhibites tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer [37]. Zhang and his colleagues showed that microRNA-7 could arrest cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells [38]. The tumor suppressive functions of miR-7 are also found in other human cancers, including cervical cancer, colorectal cancer, breast cancer, gastric cancer, tongue squamous cell carcinoma cells and glioblastoma [39-44].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma

Cheng

Shen

et al. 2017

Cell Physiol Biochem

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Background: Previously, microRNA (miR)-7 has been reported to function as a tumor suppressor in human cancers, but the correlations of miR-7 expression with prognosis and cisplatin (CDDP) resistance in lung adenocarcinoma (LA) are unclear. Here, our aim is to determine the prognostic significance of miR-7 and its roles in the regulation of CDDP resistance in LA. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to determine miR-7 expression in 108 paired of LA tissues and analyze its correlations with clinicopathological factors of patients. The patient survival data were collected retrospectively by Kaplan-Meier analyses, and multivariate analysis was performed using the Cox proportional hazards model to determine the prognostic significance of miR-7 expression. The effects of miR-7 expression on the chemosensitivity of LA cells to CDDP and its possible mechanisms were evaluated by MTT, flow cytometry, Western blot and luciferase assays. Results: It was observed that the relative expression level of miR-7 in LA tissues was significantly lower than that in the adjacent normal tissues and low miR-7 expression level was closely associated with poorer tumor differentiation, advanced pathological T-factor, higher incidence of lymph node metastasis and advanced p-TNM stage. Also, patients with low miR-7 expression showed a shorter overall survival than those with high miR-7 expression, and multivariate analysis indicated that status of miR-7 expression was an independent molecular biomarker for predicting the overall survival (OS) of LA patients. In addition, upregulation of miR-7 increases the sensitivity of LA cells to CDDP via induction of apoptosis by targeting Bcl-2. Conclusions: Our finding for the first time demonstrates that low miR-7 expression may be an independent poor prognostic factor and targeting miR-7 may be a potential strategy for the reversal of CDDP resistance in LA.

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“…[42][43][44] MiR-7 directly silences the cyclin E1 (CCNE1) gene, and CCNE1 forms a complex with and functions as a regulatory subunit of CDK2, which is required for G1 to S transition. 49 Therefore, the overexpression of miR-7 arrests the cell cycle in HCC. In addition, miR-7 binds at the 3 0 UTR of CUL5, inhibiting colony formation and inducing G1/S phase arrest.…”

Section: Roles Of Circrnas In the Oncogenesis And The Malignant Behavmentioning

confidence: 99%

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

2016

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Circular RNAs (circRNAs) are long, non-coding RNAs that result from the non-canonical splicing of linear premRNAs. However, the characteristics and the critical role of circRNA in co-/post-transcriptional regulation were not well recognized until the "microRNA sponge" function of circRNA is discovered. Recent studies have mainly been devoted to the function of the circular RNA sponge for miR-7 (ciRS-7) and sex-determining region Y (SRY) by targeting microRNA-7 (miR-7) and microRNA-138 (miR-138), respectively. In this review, we illustrate the specific role of circRNAs in a wide variety of cancers and in regulating the biological behavior of cancers via miR-7 or miR-138 regulation. Furthermore, circRNA, together with its gene silencing ability, also shows its potential in RNA interference (RNAi) therapy by binding to target RNAs, which provides a novel perspective in cancer treatment. Thus, this review concerns the biogenesis, biological function, oncogenesis, progression and possible therapies for cancer involving circRNAs.

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MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells

Cited by 99 publications

References 38 publications

TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors

TRAP1 Is Involved in BRAF Regulation and Downstream Attenuation of ERK Phosphorylation and Cell-Cycle Progression: A Novel Target for BRAF-Mutated Colorectal Tumors

Prognostic Significance of microRNA-7 and its Roles in the Regulation of Cisplatin Resistance in Lung Adenocarcinoma

Circular RNA participates in the carcinogenesis and the malignant behavior of cancer

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