KLF5 regulates epithelial-mesenchymal transition of liver cancer cells in the context of p53 loss through miR-192 targeting of ZEB2

Sun, Li; Zhou, Xiaona; Li, Yanmeng; Chen, Wei; Wu, Sha; Zhang, Bei; Yao, Jingwen; Xu, Anjian

doi:10.1080/19336918.2020.1826216

Cited by 10 publications

(17 citation statements)

References 39 publications

(66 reference statements)

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“…KLF5 has been associated with cancer cell invasion, migration and EMT progression (Zhang et al, 2013;Ma et al, 2017). Sun L et al, found that the function of KLF5 in EMT and migration of liver cancer cells depended on the p53 status (Sun et al, 2020). KLF5 promotes migration and invasion by upregulating the transcription of TNFAIP2, a tumor necrosis factor-α (TNFα)-induced gene in breast cancer cells (Jia et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

et al. 2020

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Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. Despite current therapeutic and surgical options, advanced EOC shows poor prognosis. Identifying novel molecular therapeutic targets is highly needed in the management of EOC. Krupple-like factor 5 (KLF5), a zinc-finger transcriptional factor, is highly expressed in a variety of cancer types. However, its role and expression in EOC is not fully illustrated. Immunohistochemical analysis was performed to assess KLF5 protein expression in 425 primary EOC samples using tissue microarray. We also addressed the function of KLF5 in EOC and its interaction with signal transducer and activator of transcription 3 (STAT3) signaling pathway. We found that KLF5 overexpressed in 53% (229/425) of EOC samples, and is associated with aggressive markers. Forced expression of KLF5 enhanced cell growth in low expressing EOC cell line, MDAH2774. Conversely, knockdown of KLF5 reduced cell growth, migration, invasion and progression of epithelial to mesenchymal transition in KLF5 expressing cell lines, OVISE and OVSAHO. Importantly, silencing of KLF5 decreased the self-renewal ability of spheroids generated from OVISE and OVSAHO cell lines. In addition, downregulation of KLF5 potentiated the effect of cisplatin to induce apoptosis in these cell lines. These data reveals the pro-tumorigenic role of KLF5 in EOC and uncover its role in activation of STAT3 signaling pathway, suggesting the importance of KLF5 as a potential therapeutic target for EOC therapy.

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Section: Discussionmentioning

confidence: 99%

Krupple-Like Factor 5 is a Potential Therapeutic Target and Prognostic Marker in Epithelial Ovarian Cancer

et al. 2020

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“…Recent results focusing on p53-promoted oncogenesis reveal yet another mechanism through which MDM2 may contribute to cancer progression; p53 can target master regulators of the epithelial-to-mesenchymal transition (EMT) through miRNA-dependent mechanisms [176][177][178] , suggesting a link to this major developmental and cancer-associated process.…”

Section: [H1] E3s In Cancer Progression and Suppressionmentioning

confidence: 99%

Ubiquitin ligases: guardians of mammalian development

Walma

Chen

Bullock

et al. 2022

Nat Rev Mol Cell Biol

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Mammalian development demands precision. Millions of molecules must be properly located in temporal order, and their function regulated, to orchestrate important steps in cell cycle progression, apoptosis, migration and differentiation, to shape developing embryos. Ubiquitin and its associated enzymes act as cellular guardians to ensure precise spatio-temporal control of key molecules during each of these important cellular processes. Loss of precision results in numerous examples of embryological disorders or even cancer. This Review discusses the crucial roles of E3 ubiquitin ligases during key steps of early mammalian development, their roles in human disease, and considers how new methods to manipulate and exploit the ubiquitin regulatory machineryfor example the development of molecular glues and PROTACsmight facilitate clinical therapy.

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“…49 When p53 is inactivated in Hep3B cells, KLF5 inhibits ZEB2 expression and EMT by promoting miR-192. 49 The defined role of KLF5 in HCC requires more studies.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

“…121 In the absence of p53, KLF5 inhibits EMT in liver cancer cells through the miR-192/ZEB2 axis. 49 miR-21 promoted prostate cancer cell migration and invasion by directly targeting KLF5. 82 Similar results were observed in hepatocellular carcinoma.…”

Section: Migration and Invasionmentioning

confidence: 99%

“…41 In addition to protein-encoding genes, KLF5 also regulates the In the context of p53 loss, KLF5 promotes miR-192 transcription, which inhibits the expression of zinc finger E-Box binding homeobox 2 (ZEB2) and EMT in liver cancer cells. 49 Additionally, KLF5 induces the transcription of miR-200 and inhibits the EMT process of epithelial cells. 50 Furthermore, KLF5 promotes miR-124, miR-145 and miR-183 transcription, therefore inhibiting pituitary adenoma cell migration and invasion.…”

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confidence: 99%

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