Downregulation of miR‑19a‑3p promotes invasion, migration and bone metastasis via activating TGF‑β signaling in prostate cancer

Wa, Qingde; Li, Li; Lin, Hong-Cheng; Peng, Xinsheng; Ren, Dong; Huang, Yan; He, Peiheng; Huang, Shuai

doi:10.3892/or.2017.6096

Cited by 46 publications

(45 citation statements)

References 43 publications

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“…MiR‐19a was reported to significantly regulate cell proliferation and migration. miR‐19a‐3p inhibits invasion, migration, and bone metastasis in prostate cancer, while in lung cancer, miR‐19a promotes cell proliferation and migration . miR‐19a‐3p also regulates the viability, migration, and invasion of trophoblast cells, because the overexpression of miR‐19a‐3p attenuated the inhibition of the cell viability, migration, and invasion under hypoxemia.…”

Section: Discussionmentioning

confidence: 99%

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Wang

Xue

2018

J Cellular Molecular Medi

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Preeclampsia (PE), a pregnancy‐specific disorder, is a leading cause of perinatal maternal‐fetal mortality and morbidity. Impaired cell migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as potential mechanisms of PE pathogenesis. Comparative analysis between PE placentas and normal placentas profiled differentially expressed miRNAs, lncRNAs, and mRNAs, including miR‐19a‐3p (miRNA), PSG10P (lncRNA), and IL1RAP (mRNA). This study was conducted to investigate their potential roles in PE pathogenesis. The expression of miR‐19a‐3p, PSG10P, and IL1RAP was examined in PE and normal placentas using RT‐qPCR. An in vitro experiment was performed in human trophoblast HET8/SVneo and TEV‐1 cells cultured in normoxic and hypoxic conditions. MiR‐19a‐3p targets were identified using Targetscan, miRanda, and PicTar analysis as well as luciferase reporter assays. The mouse model of PE was conducted using sFlt‐1 for in vivo tests. Lower levels of miR‐19a‐3p, but higher levels of PSG10P and IL1RAP were observed in PE placentas and the trophoblast cells in hypoxia. Luciferase reporter assays confirmed that PSG10P and IL1RAP were both direct targets of miR‐19a‐3p. Exposure to hypoxia inhibited cell viability, migration, and invasion of HET8/SVneo and TEV‐1 cells. Knocking out PSG10P and IL1RAP or overexpressing miR‐19a‐3p rescued the inhibition caused by hypoxia. In vivo experiments showed that IL1RAP promoted the expression of caspase‐3, a key apoptosis enzyme, but inhibited MMP9, which is responsible for degrading the extracellular matrix, suggesting a significant role of IL1RAP in cell proliferation, migration, and invasion. miR‐19a‐3p, PSG10P, and IL1RAP were all found to be involved in PE pathogenesis. With a common targeting region in their sequences, a regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway may contribute to PE pathogenesis during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Wang

Xue

2018

J Cellular Molecular Medi

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“…Specifically, a miR-331-3p-induced decrease of NRP2 and NACC1 results in upregulations of TGF-β1 and SMAD4, triggering EMT of prostate cancer cells [323]. Furthermore, loss of tumor suppressive miR-19a-3p leads to activation of SMAD2 and SMAD4, contributing to the formation of bone metastasis in a mouse model [324]. Loss of miR-132/212 in prostate cancer results in upregulation of targeted SOX4, thereby contributing to activation of TGF-β signaling and induction of EMT.…”

Section: Prostate Cancermentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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“…Then the expression of DLX1 in PCa samples and normal control samples from the TCGA database was analysed and the results revealed that there was a high expression in DLX1 in PCa samples (Figure E). It has been reported that DLX1 could influence disease development via the TGF‐β/Smad4 signalling pathway and the TGF‐β/Smad4 signalling pathway was previously found to be associated with PCa . Hence, there is a high possibility that DLX1 could affect the development of PCa through the TGF‐β/Smad4 signalling pathway.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‐539 functions as a tumour suppressor in prostate cancer via the TGF‐β/Smad4 signalling pathway by down‐regulating DLX1

Sun

Fan

Yang

et al. 2019

J Cellular Molecular Medi

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Prostate cancer (PCa) is the second leading cause of cancer‐related death in males, primarily due to its metastatic potential. The present study aims to identify the expression of microRNA‐539 (miR‐539) in PCa and further investigate its functional relevance in PCa progression both in vitro and in vivo. Initially, microarray analysis was conducted to obtain the differentially expressed gene candidates and the regulatory miRNAs, after which the possible interaction between the two was determined. Next, ectopic expression and knock‐down of the levels of miR‐539 were performed in PCa cells to identify the functional role of miR‐539 in PCa pathogenesis, followed by the measurement of E‐cadherin, vimentin, Smad4, c‐Myc, Snail1 and SLUG expression, as well as proliferation, migration and invasion of PCa cells. Finally, tumour growth was evaluated in nude mice through in vivo experiments. The results found that miR‐539 was down‐regulated and DLX1 was up‐regulated in PCa tissues and cells. miR‐539 was also found to target and negatively regulate DLX1 expression, which resulted in the inhibition of the TGF‐β/Smad4 signalling pathway. Moreover, the up‐regulation of miR‐539 or DLX1 gene silencing led to the inhibition of PCa cell proliferation, migration, invasion, EMT and tumour growth, accompanied by increased E‐cadherin expression and decreased expression of vimentin, Smad4, c‐Myc, Snail1 and SLUG. In conclusion, the overexpression of miR‐539‐mediated DLX1 inhibition could potentially impede EMT, proliferation, migration and invasion of PCa cells through the blockade of the TGF‐β/Smad4 signalling pathway, highlighting a potential miR‐539/DLX1/TGF‐β/Smad4 regulatory axis in the treatment of PCa.

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Downregulation of miR‑19a‑3p promotes invasion, migration and bone metastasis via activating TGF‑β signaling in prostate cancer

Cited by 46 publications

References 43 publications

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

Potential regulatory network in the PSG10P/miR‐19a‐3p/IL1RAP pathway is possibly involved in preeclampsia pathogenesis

TGF-β and microRNA Interplay in Genitourinary Cancers

MicroRNA‐539 functions as a tumour suppressor in prostate cancer via the TGF‐β/Smad4 signalling pathway by down‐regulating DLX1

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