MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

Werner, Tamara V.; Hart, Martin; Nickels, Ruth M.; Kim, Yoo-Jin; Menger, Michael D.; Bohle, Rainer M.; Keller, Andreas; Ludwig, Nicole; Meese, Eckart

doi:10.18632/aging.101201

Cited by 42 publications

(39 citation statements)

References 58 publications

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“…Accumulating evidence shows that the induction of apoptosis and activation of Wnt/ β-Catenin signaling pathways dramatically suppress tumor growth, metastasis, and chemoresistance, confirming that miR-34a can regulate apoptosis through Wnt/β-catenin signaling pathways. Indeed, some studies have revealed that miR34a alters apoptosis via direct BCL2 targeting [33,34]. Our findings clearly indicate that the overexpression of miR-34a can significantly enhance EPI-induced apoptosis and Wnt/ β-Catenin signaling pathway inhibition.…”

Section: Discussionsupporting

confidence: 60%

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chemoresistance is largely responsible for relapses of bladder cancer during clinical therapy. However, the molecular mechanisms involved in the chemoresistance of bladder cancer are unclear. Growing evidence supports the theory that microRNAs (miRNAs) play an important role in chemotherapeutic drug resistance because they are downregulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. More specifically, the extent and precise mechanism of the involvement of miR-34as in chemoresistance to epirubicin (EPI) in the treatment of bladder cancer remains unclear. Methods: In this study, real-time quantitative polymerase chain reaction (PCR) was used to analyze the expression of miR-34a in bladder cancer cell line BIU87 and its EPI chemoresistant cell line BIU87/ADR. The miR-34a profiles in bladder cancer tissues were obtained from The Cancer Genome Atlas database. The effect of miR-34a on chemosensitivity was evaluated by cell viability assays, colony formation assays, and in vivo experimentation. Apoptosis and the cell cycle were examined by flow cytometry. A luciferase reporter assay was used to assess the target genes of miR-34a. Western blot and qPCR were used to analyze the expression of target proteins and downstream molecules. Results: The downregulation of miR-34a in bladder cancer serves as an independent predictor of reduced patient survival. The CCK-8 assay showed that miR-34a overexpression resulted in increased sensitivity to EPI, while miR-34a downregulation resulted in chemoresistance to EPI in vitro. Moreover, it was found that miR-34a increased the sensitivity of BIU87/ADR cells to chemotherapy in vivo. The luciferase reporter assay ascertained that TCF1 and LEF1 are direct target genes of miR-34a. It was found that miR-34a increased chemosensitivity in BIU87/ADR cells by inhibiting the TCF1/LEF1 axis. Conclusions: The results of this study indicate that miR-34a contributes to the chemosensitivity of BIU87/ADR by inhibiting the TCF1/LEF1 axis. Consequently, miR-34a is a determinant of BIU87 chemosensitivity and may therefore serve as a potential therapeutic target in bladder cancer treatment.

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Section: Discussionsupporting

confidence: 60%

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis

Liu

et al. 2018

Cell Physiol Biochem

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“…However, one should remember that specific miRNAs can simultaneously produce competing oncogenic and tumor suppressive effects and an overall net oncogenic or net tumor-suppressive effect of miRNA may depend on the balance between miRNA-mediated upregulation or downregulation of oncogenic and tumor-suppressive pathways, the effects of the miRNA on cancer-immune system interactions and a plethora of other tumor-modifying extrinsic factors [51] . Most of upregulated miRNAs in DNMT2-silenced fibroblasts have been reported to suppress cell proliferation and promote multiple antitumor effects in different cancer models [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] . For example, miR-28-5p inhibited proliferation and migration by directly inhibiting RAP1B, a Ras-related small GTP-binding oncoprotein, in renal cell carcinoma [52] ; miR-34a-3p reduced the proliferation of meningioma cells by targeting SMAD4, FRAT1 and BCL2 [54] ; miR-30b-5p limited cell proliferation, metastasis and epithelial-to-mesenchymal transition by targeting G-protein subunit α-13 in renal cell carcinoma [55] and miR-30b-5p repressed cell proliferation by targeting DNMT3A in hepatocellular carcinoma [56] ; miR-409-3p inhibited gastric cancer cell proliferation and promoted apoptosis by targeting the transcriptional regulator PHF10 [61] and miR-409-3p suppressed breast cancer cell growth and invasion by targeting Akt1 [62] .…”

Section: Discussionmentioning

confidence: 99%

Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression

et al. 2018

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Methyltransferase DNMT2 is suggested to be involved in the regulation of numerous processes, however its biological significance and underlying molecular mechanisms remain elusive. In the present study, we have used WI-38 and BJ human fibroblasts as an in vitro model system to investigate the effects of siRNA-based DNMT2 silencing. DNMT2-depleted cells were found to be sensitive to oxidative stress conditions as judged by increased production of reactive oxygen species and susceptible to DNA damage that resulted in the inhibition of cell proliferation. DNMT2 silencing promoted upregulation of proliferation-related and tumor suppressor miRNAs, namely miR-28-3p, miR-34a-3p, miR-30b-5p, miR-29b-3p, miR-200c-3p, miR-28-5p, miR-379-5p, miR-382-5p, miR-194-5p, miR-193b-3p and miR-409-3p. Moreover, DNMT2 silencing induced cellular senescence and DNMT2 levels were elevated in replicatively senescent cells. Taken together, we found that DNMT2 may take part in the regulation of cell proliferation and longevity in human fibroblasts and speculate that the manipulation of DNMT2 levels that limits cell proliferation may be potentially useful anticancer strategy.

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“…Similarly, in meningioma, miR-34a-3p was indicated to modulate cell proliferation and apoptosis by targeting BCL2. 31 Finally, the relationship among NEAT1, miR-34a-5p, and BCL2 was explored, and it was found that downregulation of NEAT1 suppressed BCL2 expression; however, this inhibitory effect was abrogated by miR-34a-5p knockdown, suggesting that NEAT1 regulated BCL2 expression by sponging miR-34a-5p.…”

Section: Discussionmentioning

confidence: 99%

NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2

Nan

Tao

et al. 2017

OTT

107

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BackgroundNuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to act as a tumor inhibitor in many cancers. However, the role of NEAT1 in the development of ovarian cancer (OC) remains far from being elaborated. Hence, the aim of this study is to investigate the expression and function of NEAT1 in OC.Materials and methodsThe expression level of NEAT1 was determined by quantitative real-time polymerase chain reaction in OC cell lines. MTT assay, caspase-3 activity assay, and flow cytometry analysis were conducted to investigate the effects of NEAT1, miR-34a-5p, or B-cell lymphoma-2 (BCL2) on OC cell proliferation and apoptosis. Luciferase reporter assay was used to confirm the interaction of NEAT1, BCL2, and miR-34a-5p in OC cells.ResultsNEAT1 was significantly upregulated in OC cell lines. NEAT1 overexpression promoted proliferation by increasing the proportion of cells in S phase and suppressed apoptosis of OC cells, while knockdown of NEAT1 had the opposite effect. In addition, NEAT1 was demonstrated to directly interact with miR-34a-5p and exert its oncogenic role in OC by negatively regulating miR-34a-5p. Moreover, miR-34a-5p could directly target BCL2 and suppressed its expression. miR-34a-5p overexpression suppressed OC cell proliferation and triggered apoptosis by targeting BCL2. Furthermore, NEAT1 knockdown suppressed BCL2 expression, while anti-miR-34a-5p dramatically abated the inhibitory effect of si-NEAT1 on BCL2 expression.ConclusionNEAT1 regulated proliferation and apoptosis of OC cells by miR-34a-5p/BCL2, providing a potential therapeutic approach for the treatment of OC patients.

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MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

Cited by 42 publications

References 58 publications

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis

MicroRNA-34a Attenuates Metastasis and Chemoresistance of Bladder Cancer Cells by Targeting the TCF1/LEF1 Axis

Reduced levels of methyltransferase DNMT2 sensitize human fibroblasts to oxidative stress and DNA damage that is accompanied by changes in proliferation-related miRNA expression

NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2

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