MicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway

Chang, Yunli; Zhou, Peijie; Wei, Lingfei; Li, Wang; Ji, Zhongzhong; Fang, Yuxiang; Gao, Wei‐Qiang

doi:10.18632/oncotarget.4447

Cited by 89 publications

(67 citation statements)

References 29 publications

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“…However, the molecular mechanisms responsible for c‐Met amplification in NSCLC patients after receiving gefitinib treatment have not been fully elucidated. Research showed that knockdown of KLF4 inhibited the PI3K/Akt signaling pathway by regulating the promoter region of p110δ in this pathway . In the present study, we observed that knockdown of KLF4 in HCC827GR cells inhibited c‐Met and Akt activation, and overexpression of KLF4 in HCC827 cells increased c‐Met and Akt activation (Figure ).…”

Section: Discussionsupporting

confidence: 62%

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

et al. 2018

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Gefitinib has been widely used in the first‐line treatment of advanced EGFR‐mutated non‐small‐cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9‐14 months of treatment. This study revealed that Krüppel‐like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c‐Met‐overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib‐resistant NSCLC cell lines without c‐Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib‐resistant NSCLC cells with c‐Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib‐sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c‐Met‐overexpressing NSCLC cells by inhibiting the expression of apoptosis‐related proteins under gefitinib treatment and activating the c‐Met/Akt signaling pathway by decreasing the inhibition of β‐catenin on phosphorylation of c‐Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c‐Met overexpression.

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Section: Discussionsupporting

confidence: 62%

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

et al. 2018

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“…However, the role of several resveratrol‐regulated miRNAs that have been implicated in prostate cancer pathophysiology is controversial. For example, while miR‐7 was found to be upregulated in CRPC tissues and was correlated with high–Gleason score tumors and lower overall survival, a recent report revealed a negative correlation between miR‐7 expression and tumor progression in prostate cancer clinical samples . Some miRNAs, namely miR‐20a and miR‐17, are predominantly claimed as oncogenic, with some sporadic studies reporting them as tumor suppressors .…”

Section: Role Of Resveratrol‐ and Resveratrol Analog–regulated Mirnasmentioning

confidence: 99%

“…As mentioned above, miRNA expression has been detected in clinical samples for prognosis, prediction, and outcome of disease. To be exact, both single miRNAs and miRNA signature classifiers have been used in prostatectomy specimens for prediction of biochemical recurrence and prognosis of aggressive disease . However, the potential of miRNAs to become the new generation of noninvasive biomarkers is enormous owing to their stable nature and easy detection in liquid biopsies.…”

Section: Clinical Relevance Of Circulating and Tissue‐resident Mirnasmentioning

confidence: 99%

Resveratrol and pterostilbene as a microRNA‐mediated chemopreventive and therapeutic strategy in prostate cancer

Kumar

Rimando

Levenson

2017

Annals of the New York Academy of Sciences

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Growing evidence indicates that deregulation of the epigenetic machinery comprising the microRNA (miRNA) network is a critical factor in the progression of various diseases, including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA-mediated health-beneficial properties, such as anti-inflammatory, cardioprotective, antioxidative, and anticancer properties. Available experimental data have suggested that dietary polyphenols may be effective miRNA-modulating chemopreventive and therapeutic agents. Moreover, noninvasive detection of changes in miRNA expression in liquid biopsies opens enormous possibilities for their clinical utilization as novel prognostic and predictive biomarkers. In our published studies, we identified resveratrol-regulated miRNA profiles in prostate cancer. Resveratrol downregulated the phosphatase and tensin homolog (PTEN)-targeting members of the oncogenic miR-17 family of miRNAs, which are overexpressed in prostate cancer. We have functionally validated the miRNA-mediated ability of resveratrol and its potent analog pterostilbene to rescue the tumor suppressor activity of PTEN in vitro and in vivo. Taken together, our findings implicate the use of resveratrol and its analogs as an attractive miRNA-mediated chemopreventive and therapeutic strategy in prostate cancer and the use of circulating miRNAs as potential predictive biomarkers for clinical development.

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“…This concept is directly supported by Liu and colleagues’ report showing that while miR-34a, a p53 target, underexpressed in CD44+ prostate cancer cells, enforced expression of miR-34a in CD44+ prostate cancer cells inhibits clonogenic expansion, tumor regeneration, and metastasis [81, 82]. Chang and colleagues show that by acting as a tumor-suppressor, microRNA-7 (miR-7)-mediated KLF4/PI3K/Akt/p21 pathway is critical for prostate cancer stem-like cells (PCSCs) stemness - A negative correlation between miR-7 expression and prostate tumor progression implicates its potential application for prostate cancer therapy [83]. Discovery of functional master regulator (MR) proteins necessary to maintain tumour cell state shed new light on breaking up the autoregulated modules (termed tumour checkpoints) by therapeutically targeting dysregulated post-translational modifications [84].…”

Section: Clinical Relevance and Implicationsmentioning

confidence: 99%

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a ″Watch-and-Wait″� Approach to Cancer

Luo

et al. 2017

CSCR

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Targeting the tumor microenvironment (TME) through which cancer stem cells (CSCs) crosstalk for cancer initiation and progression, may open up new treatments different from those centered on the original hallmarks of cancer genetics thereby implying a new approach for suppression of TME-driven activation of CSCs. Cancer is dynamic, heterogeneous, evolving with the TME and can be influenced by tissue-specific elasticity. One of the mediators and modulators of the crosstalk between CSCs and mechanical forces is miRNA, which can be developmentally regulated, in a tissue- and cell-specific manner. Here, based on our previous data, we provide a framework through which such gene expression changes in response to external mechanical forces can be understood during cancer progression. Recognizing the ways mechanical forces regulate and affect intracellular signals with applications in cancer stem cell biology. Such TME-targeted pathways shed new light on strategies for attacking cancer stem cells with fewer side effects than traditional gene-based treatments for cancer, requiring a “watch-and-wait” approach. We attempt to address both normal brain microenvironment and tumor microenvironment as both works together, intertwining in pathology and physiology – a balance that needs to be maintained for the “watch-and-wait” approach to cancer. Thus, this review connected the subjects of tissue elasticity, tumor microenvironment, epigenetic of miRNAs, and stem-cell biology that are very relevant in cancer research and therapy. It attempts to unify apparently separate entities in a complex biological web, network, and system in a realistic and practical manner, i.e., to bridge basic research with clinical application.

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MicroRNA-7 inhibits the stemness of prostate cancer stem-like cells and tumorigenesis by repressing KLF4/PI3K/Akt/p21 pathway

Cited by 89 publications

References 29 publications

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

Krüppel‐like factor 4 promotes c‐Met amplification‐mediated gefitinib resistance in non‐small‐cell lung cancer

Resveratrol and pterostilbene as a microRNA‐mediated chemopreventive and therapeutic strategy in prostate cancer

Tissue Elasticity Bridges Cancer Stem Cells to the Tumor Microenvironment Through microRNAs: Implications for a ″Watch-and-Wait″� Approach to Cancer

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