MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

Wang, Feiran; Qiang, Yong; Zhu, Liangjun; Jiang, Yasu; Wang, Yinda; Shao, Xian; Yin, Lei; Chen, Jiahui; Chen, Zhong

doi:10.1007/s13277-016-4836-1

Cited by 47 publications

(39 citation statements)

References 38 publications

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“…Furthermore, by the multivariate analysis, we found that overexpression of VDAC1 protein in BC tissues could be as an independent poor prognostic factor. Consistent with this result, Chih-Hsien and Eiran's studies also showed that high expression of VDAC1 was correlated with poorer prognosis in uterine cervical cancer and hepatocellular carcinoma [16,17]. Therefore, these data suggest that VDAC1 has the potential of being a poor prognostic marker in BC.…”

Section: Discussionsupporting

confidence: 66%

“…It has been proved that VDAC1 involved in several diseases, such as neurodegenerative, cardiac injury and neoplastic [15]. Several studies have demonstrated remarkable expression levels of VDAC1 in malignant tumors, such as uterine cervical cancer [16], hepatocellular carcinoma [17] and Cholangiocellular Carcinoma [18], pointing to its signi cance in high energy-demanding cancer cells. VDAC1 has also been reported to promote tumor growth and play a controversial role in the prognosis of different cancers [19].…”

Section: Introductionmentioning

confidence: 99%

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VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Chen

Yin

Luo

et al. 2020

Preprint

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AIM: The main objectives of this article were to evaluate the association of voltage-dependent anion channel 1 (VDAC1) expression with Cytochrome C (Cytc) protein, various clinicopathological features and prognosis in patients diagnosed with breast cancer (BC). Meanwhile, the correlation of Cytc expression with various clinical features and 5-year disease-free survival (5-DFS) of BC is also investigated. Methods: Expression of VDAC1 protein and Cytc protein was conducted in 219 BC patients and 60 benign breast lesions by immunohistochemical (IHC) analysis. Results: In our study, VDAC1 protein expression was significantly increased while Cytc protein was decreased in breast tumor tissues (P = 0.015 and P = 0.029, respectively). High expression of VDAC1 is conversely associated with Cytc expression in BC, especially in triple-negative breast cancer (TNBC) (P = 0.011 and P = 0.004, respectively). Interestingly, high expression of VDCA1 not only had a significant association with advanced TNM stage, histological grade, LNM, HER2 gene amplification and recurrence (P < 0.05), but also displayed a poorer 5-DFS (P < 0.001) in BC. The multivariate Cox proportional hazard model demonstrated VDAC1 as a novel independent poor prognostic factor in BC (P = 0.001). Strikingly, our study also showed the prognostic significance of VDAC1 in triple-negative breast cancer in particular. Furthermore, low expression of Cytc was found to be correlated with histological grade, ER status, PR status and recurrence in BC (P < 0.05). Kaplan-Meier analysis indicated that low Cytc expression was associated with poorer survival and high mortality rate (P = 0.007). Cytc protein expression also served as a novel independent prognosis parameters in BC patients (P = 0.035). Conclusion: Our findings firstly revealed that VDAC1 was elevated in BC tissues and conversely associated with Cytc. Furthermore, high VDAC1 protein was associated with reduced 5-DFS and could be acted as an independent poor prognostic factor not only in breast cancer in general, but also in TNBC in particular. All in all, VDAC1 can be exploited as a potential prognostic marker and therapeutic target in BC, especially in TNBC.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Chen

Yin

Luo

et al. 2020

Preprint

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“…The 3′-UTR sequence may be a target of translation regulation by miRNA or interference. Many publications indeed reported the identification of miRNA molecules targeting all three VDACs transcripts but, in particular, VDAC1 [ 73 ]. The 5′-UTR region variability might be associated with alternative promoter usage and activation in a different expression context.…”

Section: Discussionmentioning

confidence: 99%

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

Zinghirino

Pappalardo

Messina

et al. 2020

IJMS

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VDACs (voltage-dependent anion-selective channels) are pore-forming proteins of the outer mitochondrial membrane, whose permeability is primarily due to VDACs’ presence. In higher eukaryotes, three isoforms are raised during the evolution: they have the same exon–intron organization, and the proteins show the same channel-forming activity. We provide a comprehensive analysis of the three human VDAC genes (VDAC1–3), their expression profiles, promoter activity, and potential transcriptional regulators. VDAC isoforms are broadly but also specifically expressed in various human tissues at different levels, with a predominance of VDAC1 and VDAC2 over VDAC3. However, an RNA-seq cap analysis gene expression (CAGE) approach revealed a higher level of transcription activation of VDAC3 gene. We experimentally confirmed this information by reporter assay of VDACs promoter activity. Transcription factor binding sites (TFBSs) distribution in the promoters were investigated. The main regulators common to the three VDAC genes were identified as E2F-myc activator/cell cycle (E2FF), Nuclear respiratory factor 1 (NRF1), Krueppel-like transcription factors (KLFS), E-box binding factors (EBOX) transcription factor family members. All of them are involved in cell cycle and growth, proliferation, differentiation, apoptosis, and metabolism. More transcription factors specific for each VDAC gene isoform were identified, supporting the results in the literature, indicating a general role of VDAC1, as an actor of apoptosis for VDAC2, and the involvement in sex determination and development of VDAC3. For the first time, we propose a comparative analysis of human VDAC promoters to investigate their specific biological functions. Bioinformatics and experimental results confirm the essential role of the VDAC protein family in mitochondrial functionality. Moreover, insights about a specialized function and different regulation mechanisms arise for the three isoform gene.

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“…Cumulative evidence indicates that miRNA serve as tumor promoters or suppressors, regulating a wide range of biologic processes, such as proliferation, apoptosis, invasion and metastasis. In particular, it has been demonstrated that miR‐203 serves as a potential tumor suppressor in HCC . In investigating the clinical implications and biological relevance of aberrant expression of miR‐203 in HCC, higher miR‐203 expression was suggested to predict better prognosis .…”

mentioning

confidence: 99%

“…In particular, it has been demonstrated that miR-203 serves as a potential tumor suppressor in HCC. (5)(6)(7)(8)(9)(10) In investigating the clinical implications and biological relevance of aberrant expression of miR-203 in HCC, higher miR-203 expression was suggested to predict better prognosis. (7,9) In HCC cell line experiments, miR-203 overexpression inhibited growth and metastasis of HCC, with potential targets including surviving, EZH2, Bmi-1 and ATP binding cassette E1.…”

mentioning

confidence: 99%

miR‐203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver

Zheng

Chen

et al. 2017

Cancer Science

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Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR‐203 adenovirus was administered to induce hepatic miR‐203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR‐203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non‐tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR‐203 overexpression further promoted the regeneration of the non‐tumorous liver by upregulating Ki67 expression and enhancing IL‐6/SOCS3/STAT3 pro‐proliferative signals. Importantly, miR‐203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR‐203 overexpression reversed the epithelial–mesenchymal transition induced by hepatectomy through targeting IL‐1β, Snail1 and Twist1. In conclusion, our results suggested that miR‐203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial–mesenchymal transition.

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MicroRNA-7 downregulates the oncogene VDAC1 to influence hepatocellular carcinoma proliferation and metastasis

Cited by 47 publications

References 38 publications

VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

VDAC1 Conversely Correlates with Cytc Expression and Predicts Poor Prognosis in Human Breast Cancer Patients

Is the Secret of VDAC Isoforms in Their Gene Regulation? Characterization of Human VDAC Genes Expression Profile, Promoter Activity, and Transcriptional Regulators

miR‐203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver

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