miR-34C Disrupts the Stemness of Purified CD133 + Prostatic Cancer Stem Cells

Chen, Yuan; Rao, Qun; Zhang, Huiping; Xu, Hua; Zhang, Cuntai; Zhuang, Qianyuan; Ye, Zhangqun

doi:10.1016/j.urology.2016.07.021

Cited by 10 publications

(8 citation statements)

References 26 publications

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“…68, 69, 77, 78, 79, 80 Some studies also demonstrated downregulation of miR-34c in breast and prostate cancer stem cells and the roles of miR-34c to suppress cancer stemness via targeting p53 and Notch genes but have never linked to AREG. 27, 81, 82 The role of miR-34c-5p in ovarian cancer stem cells has never been reported before and information on its regulatory role on AREG is also lacking. In this study, we demonstrated that miR-34c-5p directly targeted and downregulated AREG to inhibit ovarian cancer stemness and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway

Tung

et al. 2017

Oncogenesis

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Epithelial ovarian cancer is the most lethal gynecological cancer mainly due to late diagnosis, easy spreading and rapid development of chemoresistance. Cancer stem cells are considered to be one of the main mechanisms for chemoresistance, as well as metastasis and recurrent disease. To explore the stemness characteristics of ovarian cancer stem cells, we successfully enriched ovarian cancer stem-like cells from an established ovarian cancer cell line (SKOV-I6) and a fresh ovarian tumor-derived cell line (OVS1). These ovarian cancer stem-like cells possess important cancer stemness characteristics including sphere-forming and self-renewing abilities, expressing important ovarian cancer stem cell and epithelial–mesenchymal transition markers, as well as increased drug resistance and potent tumorigenicity. Microarray analysis of OVS1-derived sphere cells revealed increased expression of amphiregulin (AREG) and decreased expression of its conserved regulatory microRNA, miR-34c-5p, when compared with the OVS1 parental cells. Overexpression of AREG and decreased miR-34c-5p expression in SKOV-I6 and OVS1 sphere cells were confirmed by quantitative real-time PCR analysis. Luciferase reporter assay and mutant analysis confirmed that AREG is a direct target of miR-34c-5p. Furthermore, AREG-mediated increase of sphere formation, drug resistance toward docetaxel and carboplatin, as well as tumorigenicity of SKOV-I6 and OVS1 cells could be abrogated by miR-34c-5p. We further demonstrated that miR-34c-5p inhibited ovarian cancer stemness through downregulation of the AREG-EGFR-ERK pathway. Overexpression of AREG was found to be correlated with advanced ovarian cancer stages and poor prognosis. Taken together, our data suggest that AREG promotes ovarian cancer stemness and drug resistance via the AREG-EGFR-ERK pathway and this is inhibited by miR-34c-5p. Targeting AREG, miR-34c-5p could be a potential strategy for anti-cancer-stem cell therapy in ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway

Tung

et al. 2017

Oncogenesis

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“…Notch1 as a target of miR‐34C is crucial to maintaining the properties of CSC. miR‐34C downregulates self‐renewal properties of CD133+ cells in prostate cancer by targeting Notch1 (Y. Chen et al, ).…”

Section: Molecular Structure and Function Of Cd133mentioning

confidence: 99%

New emerging roles of CD133 in cancer stem cell: Signaling pathway and miRNA regulation

Aghajani

Mansoori

Mohammadi

et al. 2019

Journal Cellular Physiology

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Cancer stem cells (CSC) are rare immortal cells within a tumor that are able to initiate tumor progression, development, and resistance. Advances studies show that, like normal stem cells, CSCs can be both self-renewed and given rise to many cell types, therefore form tumors. A number of cell surface markers, such as CD44, CD24, and CD133 are frequently used to identify CSCs. CD133, a transmembrane glycoprotein, either alone or in collaboration with other markers, has been mainly considered to identify CSCs from different solid tumors. However, the exactness of CD133 as a cancer stem cell biomarker has not been approved yet. The clinical importance of CD133 is as a CSC marker in many cancers. Also, it contributes to shorter survival, tumor progression, and tumor recurrence. The expression of CD133 is controlled by many extracellular or intracellular factors, such as tumor microenvironment, epigenetic factors, signaling pathways, and miRNAs. In this study, it was attempted to determine: 1) CD133 function; 2) the role of CD133 in cancer; 3) CD133 regulation; 4) the therapeutic role of CD133 in cancers.

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“…Another pathway explored for PCaSCs maintenance is the suppression of p27, caused for instance, by increased miR-150 expression, that might participate in the development and progression of PCaSCs (Liu et al, 2015). It has also been shown that downregulation of miR-34c in cancer stem cells causes recurrence of PCa (Chen et al, 2016).…”

Section: The Cancer Stem-like Statementioning

confidence: 99%

MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness

et al. 2019

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MicroRNAs (miRNAs) are small non-coding RNA molecules that play key regulatory roles in cancer acting as both oncogenes and tumor suppressors. Due to their potential roles in improving cancer prognostic, predictive, diagnostic and therapeutic approaches, they have become an area of intense research focus in recent years. Several studies have demonstrated an altered expression of several miRNAs under hypoxic condition and even shown that the hypoxic microenvironment drives the selection of a more aggressive cancer cell population through cellular adaptations referred as the cancer stem-like cell. These minor fractions of cells are characterized by their self-renewal abilities and their ability to maintain the tumor mass, suggesting their crucial roles in cancer development. This review aims to highlight the interconnected role between miRNAs, hypoxia and the stem-like state in contributing to the cancer aggressiveness as opposed to their independent contributions, and it is based in four aggressive tumors, namely glioblastoma, cervical, prostate, and breast cancers.

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miR-34C Disrupts the Stemness of Purified CD133 + Prostatic Cancer Stem Cells

Cited by 10 publications

References 26 publications

miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway

miRNA-34c-5p inhibits amphiregulin-induced ovarian cancer stemness and drug resistance via downregulation of the AREG-EGFR-ERK pathway

New emerging roles of CD133 in cancer stem cell: Signaling pathway and miRNA regulation

MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness

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