Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR-145

Ren, Dong; Wang, Min; Guo, Wei; Zhao, Xiaohui; Tu, Xiang-An; Huang, Shuai; Zou, Xuenong; Peng, Xinsheng

doi:10.3892/ijo.2013.1825

Cited by 122 publications

(102 citation statements)

References 44 publications

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“…Our observation was closely consistent with a recently published report demonstrating that UCA1 promoted bladder cancer cell migration and invasion by the hsa-mir145-ZEB1/2-FSCN1 pathway (24). Similar to miR-143, miR-145 was also reported to be a tumor suppressive gene and a negative regulator of EMT (47)(48)(49). Thus, UCA1 might function as an oncogene by sponging EMT-related miRNAs.…”

Section: Discussionsupporting

confidence: 81%

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

Luo

Chen

et al. 2017

Oncol Lett

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Abstract. The long non-coding RNA (lncRNA) urothelial carcinoma associated 1 (UCA1) is an oncogenic lncRNA in bladder cancer, and its upregulation is associated with enhanced cell invasion. However, the underlying mechanism remains to be elucidated. The present study demonstrated that UCA1 was positively associated with cell invasion ability and promoted epithelial-mesenchymal transition (EMT) of bladder cancer cells by inducing high mobility group box 1 (HMGB1). Furthermore, bioinformatics and luciferase reporter assays demonstrated binding sites of the tumor suppressive miR-143 within UCA1 and the 3'untranslated region of HMGB1. UCA1 negatively regulated miR-143 expression in a dose-dependent manner in bladder cancer cells. In addition, UCA1 and HMGB1 were upregulated and miR-143 was downregulated in bladder cancer specimens. Overall, the data suggested that UCA1 may promote the invasion and EMT of bladder cancer cells by regulating the miR-143/HMGB1 pathway, which exhibits an important regulatory role in the pathology of bladder cancer.

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Section: Discussionsupporting

confidence: 81%

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

Luo

Chen

et al. 2017

Oncol Lett

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“…Interestingly, Sachdeva and colleagues showed that p53 directly binds the promoter of miR145 at the p53 response element region (48). p53 was shown to suppress EMT and TICs properties by upregulating miR145 (49). These data suggest a possible mechanism that curcumin, by inducing the expression of p53, could increase the expression of miR145 in HNC-TICs.…”

Section: Cd44mentioning

confidence: 91%

miR145 Targets the SOX9/ADAM17 Axis to Inhibit Tumor-Initiating Cells and IL-6–Mediated Paracrine Effects in Head and Neck Cancer

et al. 2013

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ALDH1þ CD44 þ cells are putative tumor-initiating cells (TIC) in head and neck squamous cell carcinomas (HNC). miR-145 regulates tumorigenicity in various cancers but the breadth of its mechanistic contributions and potential therapeutic applications are not completely known. Here, we report that ALDH1 þ CD44 þ -HNC cells express reduced levels of miR145. SPONGE-mediated inhibition of miR-145 (Spg-miR145) was sufficient to drive tumor-initiating characteristics in non-TICs/ALDH1 À CD44-negative HNC cells. Mechanistic analyses identified SOX9 and ADAM17 as two novel miR145 targets relevant to this process. miR-145 expression repressed TICs in HNC in a manner associated with SOX9 interaction with the ADAM17 promoter, thereby activating ADAM17 expression. Notably, the SOX9/ADAM17 axis dominated the TIC-inducing activity of miR-145. Either miR-145 suppression or ADAM17 overexpression in non-TICs/ALDH1À CD44 À -HNC cells increased expression and secretion of interleukin (IL)-6 and soluble-IL-6 receptor (sIL-6R). Conversely, conditioned medium from SpgmiR145-transfected non-TICs/ALDH1 À CD44 À -HNC cells was sufficient to confer tumor-initiating properties in non-TICs/ALDH1À CD44 À -HNC and this effect could be abrogated by an IL-6-neutralizing antibody. We found that curcumin administration increased miR-145 promoter activity, thereby decreasing SOX9/ADAM17 expression and eliminating TICs in HNC cell populations. Delivery of lentivral-miR145 or orally administered curcumin blocked tumor progression in HNC-TICs in murine xenotransplant assays. Finally, immunohistochemical analyses of patient specimens confirmed that an miR-145 low /SOX9 high /ADAM17 high phenotype correlated with poor survival. Collectively, our results show how miR-145 targets the SOX9/ADAM17 axis to regulate TIC properties in HNC, and how altering this pathway may partly explain the anticancer effects of curcumin. By inhibiting IL-6 and sIL-6R as downstream effector cytokines in this pathway, miR-145 seems to suppress a paracrine signaling pathway in the tumor microenvironment that is vital to maintain TICs in HNC. Cancer Res; 73(11); 3425-40. Ó2013 AACR.

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“…Our data are consistent with previous studies showing that PI3K/Akt inhibitor or resveratrol treatment inhibits p-Akt and induces miR-145. Although several transcription factors, such as Foxo and p53, have been implicated in the regulation of miR-145, the silencing of miR-145 in many cancers is not clearly understood (Gan et al 2010, Ren et al 2013. The specific inhibition of the PI3K/Akt pathway has been recently reported to lead to upregulation of miR-145 in a p53-dependent manner (Sachdeva et al 2009).…”

Section: Discussionmentioning

confidence: 99%

miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

Boufraqech¹,

Zhang²,

Jain³

et al. 2014

Endocrine-Related Cancer

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The expression and function of miR-145 in thyroid cancer is unknown. We evaluated the expression and function of miR-145 in thyroid cancer and its potential clinical application as a biomarker. We found that the expression of miR-145 is significantly downregulated in thyroid cancer as compared with normal. Overexpression of miR-145 in thyroid cancer cell lines resulted in: decreased cell proliferation, migration, invasion, VEGF secretion, and E-cadherin expression. miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF secretion. miR-145 inhibition in normal primary follicular thyroid cells decreased the expression of thyroid cell differentiation markers. Analysis of indeterminate fine-needle aspiration samples showed miR-145 had a 92% negative predictive value for distinguishing benign from malignant thyroid nodules. Circulating miR-145 levels were significantly higher in patients with thyroid cancer and showed a venous gradient. Serum exosome extractions revealed that miR-145 is secreted. Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.

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Wild-type p53 suppresses the epithelial-mesenchymal transition and stemness in PC-3 prostate cancer cells by modulating miR-145

Cited by 122 publications

References 44 publications

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

LncRNA UCA1 promotes the invasion and EMT of bladder cancer cells by regulating the miR‑143/HMGB1 pathway

miR145 Targets the SOX9/ADAM17 Axis to Inhibit Tumor-Initiating Cells and IL-6–Mediated Paracrine Effects in Head and Neck Cancer

miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3

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