MicroRNA-34a Suppresses Cell Proliferation by Targeting LMTK3 in Human Breast Cancer MCF-7 Cell Line

Zhao, Guoqing; Guo, Jun; Li, Dong; Jia, Chengyou; Yin, Wen; Sun, Rong; Lv, Zhongwei; Cong, Xianling

doi:10.1089/dna.2013.2130

Cited by 42 publications

(36 citation statements)

References 20 publications

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“…miR-34a was reported to inhibit breast cancer cell proliferation by inhibiting the Akt signaling pathway [48]. Restoration of miR-34a reduces breast cancer proliferation and migration through regulation of Bcl-2 [19].…”

Section: Discussionmentioning

confidence: 99%

Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis

Guo

Bledsoe

et al. 2016

Experimental Cell Research

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Kallistatin is an endogenous protein that regulates differential signaling pathways and biological functions. Our previous studies showed that kallistatin gene therapy inhibited angiogenesis, tumor growth and metastasis in mice, and kallistatin protein suppressed Wnt-mediated growth, migration and invasion by blocking Wnt/β-catenin signaling pathway in breast cancer cells. In this study, we show that kallistatin reduced cell viability, and increased apoptotic cell death and caspase-3 activity in MDA-MB-231 breast cancer cells. Kallistatin also induced cancer cell autophagy, as evidenced by increased LC3B levels and elevated Atg5 and Beclin-1 expression; however, co-administration of Wnt or PPARγ antagonist GW9662 abolished these effects. Moreover, kallistatin via its heparin-binding site antagonized Wnt3a-induced cancer cell proliferation and increased PPARγ expression. Kallistatin inhibited oncogenic miR-21 synthesis associated with reduced Akt phosphorylation and Bcl-2 synthesis, but increased BAX expression. Kallistatin via PKC-ERK activation reduced miR-203 levels, leading to increased expression of suppressor of cytokine signaling 3 (SOCS3), a tumor suppressor. Conversely, kallistatin stimulated expression of the tumorigenic suppressors miR-34a and p53. Kallistatin’s active site is essential for suppressing miR-21 and miR-203, and stimulating miR-34a and SOCS3 expression. This is the first study to demonstrate that kallistatin’s heparin-binding site is essential for inhibiting Wnt-mediated effects, and its active site plays a key role in regulating miR-21, miR-203, miR-34a and SOCS3 synthesis in breast cancer cells. These findings reveal novel mechanisms of kallistatin in inducing apoptosis and autophagy in breast cancer cells, thus inhibiting tumor progression by regulation of Wnt/PPARγ signaling, as well as miR-21, miR-203 and miR-34a synthesis.

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Section: Discussionmentioning

confidence: 99%

Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis

Guo

Bledsoe

et al. 2016

Experimental Cell Research

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“…56 Treating ERα-positive breast cancer cell line MCF-7 with estrogen, results in downregulation of miR-34a. However, enforced expression of miR-34a, using lentiviral vector, causes downregulation of LMTK3 and reduces Akt phosphorylation.…”

Section: Mir-34a Targetsmentioning

confidence: 99%

Mir-34: A New Weapon Against Cancer?

Misso

Martino

Rosa

et al. 2014

Molecular Therapy - Nucleic Acids

442

374

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The microRNA(miRNA)-34a is a key regulator of tumor suppression. It controls the expression of a plethora of target proteins involved in cell cycle, differentiation and apoptosis, and antagonizes processes that are necessary for basic cancer cell viability as well as cancer stemness, metastasis, and chemoresistance. In this review, we focus on the molecular mechanisms of miR-34a-mediated tumor suppression, giving emphasis on the main miR-34a targets, as well as on the principal regulators involved in the modulation of this miRNA. Moreover, we shed light on the miR-34a role in modulating responsiveness to chemotherapy and on the phytonutrients-mediated regulation of miR-34a expression and activity in cancer cells. Given the broad anti-oncogenic activity of miR-34a, we also discuss the substantial benefits of a new therapeutic concept based on nanotechnology delivery of miRNA mimics. In fact, the replacement of oncosuppressor miRNAs provides an effective strategy against tumor heterogeneity and the selective RNA-based delivery systems seems to be an excellent platform for a safe and effective targeting of the tumor.

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“…In ERα + , estradiol-treated breast cancer cells, overexpression of miR-34a via a lentivirus suppressed cell proliferation, S phase ratio, and tumor formation[43]. MiR-34a is also involved in sensitizing ERα + breast cancer cells to frontline therapeutic agents ( See Table 2).…”

Section: The Tumor-suppressive Role Of Mir-34a In Solid Tumorsmentioning

confidence: 99%

The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas

Adams

Parsons

Slack

2015

Expert Opinion on Therapeutic Targets

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Introduction Many RNA species have been identified as important players in the development of chronic diseases including cancer. Certain classes of regulatory RNAs such as miRNAs have been investigated in such detail that bona fide tumor suppressive and oncogenic miRNAs have been identified. Because of this, there has been a major effort to therapeutically target these small RNAs. One in particular, a liposomal formulation of miR-34a (MRX34), has entered Phase I trials. Areas Covered This review aims to summarize miRNA biology, its regulation within normal versus disease states, and how it can be targeted therapeutically, with a particular emphasis on miR-34a. Understanding the complexity of a single miRNA will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases. Expert Opinion The potential of miRNAs to be developed into anti-cancer therapeutics has become an increasingly important area of research. miR-34a is a tumor suppressive miRNA across many tumor types through its ability to inhibit cellular proliferation, invasion, and tumor sphere formation. miR-34a also shows promise within certain in vivo solid tumor models. Finally, as miR-34a moves into clinical trials it will be important to determine if it can further sensitize tumors to certain chemotherapeutic agents.

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MicroRNA-34a Suppresses Cell Proliferation by Targeting LMTK3 in Human Breast Cancer MCF-7 Cell Line

Cited by 42 publications

References 20 publications

Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis

Kallistatin induces breast cancer cell apoptosis and autophagy by modulating Wnt signaling and microRNA synthesis

Mir-34: A New Weapon Against Cancer?

The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas

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