Silencing Bmi-1 enhances the senescence and decreases the metastasis of human gastric cancer cells

Gao, Fenglan; Li, Weishan; Liu, Chunling; Zhao, Guoqiang

doi:10.3748/wjg.v19.i46.8764

Cited by 14 publications

(11 citation statements)

References 18 publications

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“…Bmi-1 was reported one of the genes inhibit cell senescence [37, 38] and inhibiting the expression of Bmi-1 could promote cell senescence [39]. Besides, Bmi-1 was a putative target of miR-495 and, so we wondered whether miR-495 correlated with Bmi-1 in MSCs.…”

Section: Resultsmentioning

confidence: 99%

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

Song

Liú

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. Abnormal proliferation and function of MSCs were reported at maternal fetal interface in patients with pre-eclampsia (PE). Micro-RNA-495 was known to be upregulated in the MSCs derived from patients with PE. However, it is not clear whether the up-regulated miR-495 is related to the pathogenesis of PE. Methods: We analyzed the expression of miR-495 in MSCs and umbilical cords derived from healthy pregnancies (NC) and PE, then we upregulated or downregulated the expression of miR-495 in MSCs derived from NC and tested the proliferation, apoptosis, migration, invasion, tube formation and senescence. Results: In the current study, we found that the expression of miR-495 was significantly increased in both umbilical cord tissues and MSCs in patients with severe PE. Overexpressing miR-495 arrested cell cycle in S phase and promoted cell apoptosis. The supernatants from miR-495-overexpressed-MSCs inhibited the migration of MSCs and HTR-8/SVneo, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-miR-495 had the opposite effects. Furthermore, we analyzed the senescence related β-galactosidase activity and CD146 and found that miR-495 induced the senescence of MSCs. Molecular mechanism studies confirmed that Bmi-1 mediated these effects of miR-495 on MSCs. Conclusion: Taken together, our data demonstrated that miR-495 induced senescence of MSCs may be involved in the pathogenesis of PE.

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Section: Resultsmentioning

confidence: 99%

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

Song

Liú

et al. 2017

Cell Physiol Biochem

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“…Subsequently, knockdown of BMI-1 can effectively inhibit tumor cell proliferation and tumorigenicity in several tumors. Silencing BMI-1 by RNA interference can promote senescence and effectively decrease metastasis of gastric cancer cells (52)(53)(54). In addition, Wu et al (55) validated that BMI-1 functions as an oncogene in osteosarcoma and enhances tumorigenicity and resistance to chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death

2016

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The B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) protein is activated in various types of tumors and associated with cancer development and tumor progression. However, the working role of BMI-1 in cellular signaling is not understood completely. In this study, we revealed one possible biologic mechanism of BMI-1 in cancer progression in vitro using a human ovarian tumor cell system. Suppressor of MEK1 (sMEK1), a pivotal regulator involved in the cellular biological response mechanism, was identified as a BMI-1-binding protein. Ectopic expression of BMI-1 activated cell growth by reducing sMEK1-stimulated apoptotic cell death and suppressing p21, p27 and p53 expression, while enhancing cyclin D1, CDK4 and Bcl-2 expression. The effect of BMI-1 on cell cycle and apoptotic regulatory proteins was also confirmed via silencing of BMI-1 expression. Subsequently, the promoter activities of p21 and p53 were inactivated significantly. However, BMI-1 overexpression noticeably increased Bcl-2 and NF-κB activities. In addition, BMI-1 activated the PI3K/mTOR/4E-BP1 signaling pathways, and sMEK1 significantly inhibited BMI-1-stimulated oncogenesis. These insights provide evidence that BMI-1 activates cell growth and suppresses apoptosis. Collectively, our data indicate that BMI-1 plays a pivotal role in the progression of ovarian cancer, thus representing a novel target for antitumor therapy of ovarian cancer.

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“…Strong evidence supports the involvement of BMI-1 in tumor cell invasion in gastric cancer, primary HCC, pancreatic cancer, endometrial carcinoma, and head and neck cancer ( Table I). Overexpression of BMI-1 in gastric cancer resulted in increased migration and invasion abilities (21,22), while BMI-1 depletion reduced the invasiveness of HCC cells (15). Song et al also identified that upregulation of BMI-1 expression enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing of BMI-1 expression reduced motility (27).…”

Section: Bmi-1 and Cancermentioning

confidence: 99%

“…The overexpression of BMI-1 in gastric and breast cancer has been identified to promote cell growth and proliferation, inhibit apoptosis and enhanced clone formation capability (6,21,22). By contrast, the depletion of BMI-1 in certain pancreatic cancer cell lines was found to suppress cell proliferation, sensitize apoptosis and inhibit tumor formation in nude mice (13,(23)(24)(25).…”

Section: Bmi-1 and Cancermentioning

confidence: 99%

BMI-1, a promising therapeutic target for human cancer

Wang

Cui

et al. 2015

Oncology Letters

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Abstract. BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types.

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Silencing Bmi-1 enhances the senescence and decreases the metastasis of human gastric cancer cells

Abstract: Silencing Bmi-1 by RNA interference can increase the senescent cell rate and effectively reduce the metastasis of gastric cancer cells.

Cited by 14 publications

References 18 publications

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

MiR-495 Promotes Senescence of Mesenchymal Stem Cells by Targeting Bmi-1

BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death

BMI-1, a promising therapeutic target for human cancer

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