Mapping the STK4/Hippo signaling network in prostate cancer cell

Ready, Damien; Yagiz, Kader; Amin, Pooneh; Yildiz, Yuksel; Funari, Vincent; Bozdag, Seardar; Cinar, Bekir

doi:10.1371/journal.pone.0184590

Cited by 25 publications

(24 citation statements)

References 60 publications

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“…Co-expression analysis indicated that circRNAs were closely correlated with certain mRNAs, some of which were reported to play vital roles in PCa, such as ZNF217 and STK4 [28,29]. Conceivably, circRNAs might influence PCa carcinogenesis via these mRNAs.…”

Section: Discussionmentioning

confidence: 94%

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Song

Zhuo

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Our study is to explore the expression profiles and potential functions of circRNAs in prostate cancer (PCa). A total of 95 circRNAs and 830 mRNAs were screened to be significantly differentially expressed in PCa tissues by microarrays. Co-expression and competitive endogenous RNA (ceRNA) network were constructed to reveal the potential regulatory mechanisms of circRNAs. Three circRNAs, hsa_circ_0001206, hsa_circ_0001633, and hsa_circ_0009061 were validated to be down-regulated in PCa by quantitative real-time PCR (qRT-PCR) and hsa_circ_0001206 as well as hsa_circ_0009061 was significantly associated with clinical features of PCa patients. Meanwhile, Receiver Operating Characteristic (ROC) curves showed their good diagnostic value as biomarkers for PCa. The down-regulation of hsa_circ_001206 was partly because of the regulation of DExH-Box Helicase 9 (DHX9). Moreover, overexpression of hsa_circ_0001206 inhibited PCa cell proliferation, migration, and invasion in vitro and prevented tumor growth in vivo. Dual-luciferase reporter assays showed hsa_circ_0001206 could directly bind to miR-1285-5p. The expression of Smad4, a well-known suppressive gene in PCa, can be increased by overexpression of hsa_circ_0001206 and this effect could be partly reversed by co-transfection of miR-1285-5p mimic. The study revealed expression profiles and potential functions of circRNAs and demonstrated hsa_circ_0001206 played a suppressive role in the pathogenesis of PCa. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 94%

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Song

Zhuo

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…8,9 In addition, existing literature has suggested that DNA hypermethylation and post-translational modification can mediate the loss of STK4 activity. 11 The Hippo signalling pathway, comprised of mammalian STE20-like protein kinase 1 and 2 (MST1/2), large tumour suppressor kinase 1/2 (LAST1/2) and its downstream transcription co-activator, Yesassociated protein (YAP), have been implicated in the regulation of tumour suppression concerning tissue repair and regeneration. 11 The Hippo signalling pathway, comprised of mammalian STE20-like protein kinase 1 and 2 (MST1/2), large tumour suppressor kinase 1/2 (LAST1/2) and its downstream transcription co-activator, Yesassociated protein (YAP), have been implicated in the regulation of tumour suppression concerning tissue repair and regeneration.…”

Section: Introductionmentioning

confidence: 99%

“…10 Ready et al concluded that the dysregulation of STK4 is linked to carcinogenesis associated with poor outcomes in addition to implicating the Hippo signalling pathway in this process. 11 The Hippo signalling pathway, comprised of mammalian STE20-like protein kinase 1 and 2 (MST1/2), large tumour suppressor kinase 1/2 (LAST1/2) and its downstream transcription co-activator, Yesassociated protein (YAP), have been implicated in the regulation of tumour suppression concerning tissue repair and regeneration. 12 Based on the exploration of the aforementioned literature, we asserted the hypothesis that lncRNA TNRC6C-AS1 could potentially work in tandem with STK4 and the Hippo signalling pathway in TC cells, whereby tumour progression can be regulated.…”

Section: Introductionmentioning

confidence: 99%

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Yang

Guo

et al. 2019

Cell Proliferation

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Objectives: Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated with a significant risk of developing hypothyroidism.In order to adequately understand the expression profiles of TNRC6C-AS1 and STK4and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted.Methods: A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C-AS1 by over-expression or silencing means. The interaction of TNRC6C-AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis.Results: TNRC6C-AS1 was up-regulated while STK4 was down-regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C-AS1, which was enriched by methyltransferase. Methyltransferase's binding to STK4 increased expression of its promoter. Over-expressed TNRC6C-AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity.Conclusion: Based on our observations, we subsequently confirmed the anti-proliferative, pro-apoptotic and pro-autophagy capabilities of TNRC6C-AS1 through STK4 methylation via the Hippo signalling pathway in TC.

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“…22 A study has showed that the protein level of STK4 decreases in the progression of prostate cancer. 23 Based on RIP assay in this study, the expression of STK4 was regulated by lncRNA TNRC6C-AS1. LncRNA TNRC6C-AS1 promoted STK4 by inhibiting the methylation of STK4 promoter, thus inhibiting the phosphorylation level of YAP and Hippo signalling pathway.…”

Section: Discussionmentioning

confidence: 76%

Long non‐coding RNA TNRC6C‐AS1 promotes methylation of STK4 to inhibit thyroid carcinoma cell apoptosis and autophagy via Hippo signalling pathway

Peng

Tan

et al. 2019

J Cellular Molecular Medi

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The role of long non‐coding RNAs (lncRNAs) in thyroid carcinoma (TC), the most frequent endocrine malignancy, has been extensively examined. This study investigated effect of interaction among lncRNA TNRC6C‐AS1, serine/threonine‐protein kinase 4 (STK4) and Hippo signalling pathway on TC. Initially, lncRNA TNRC6C‐AS1 expression in TC tissues was detected. To explore roles of lncRNA TNRC6C‐AS1, STK4 and Hippo signalling pathway in TC progression, their expressions were altered. Interaction between lncRNA TNRC6C‐AS1 and STK4, STK4 promoter methylation, or Hippo signalling pathway was verified. After that, a series of experiments were employed to evaluate in vitro ability of apoptosis, proliferation and autophagy of TC cells and in vivo tumorigenicity, and tumour growth of TC cells. lncRNA TNRC6C‐AS1 was highly expressed while STK4 was poorly expressed in TC tissues. LncRNA TNRC6C‐AS1 promoted the STK4 methylation and down‐regulated STK4 expression, which further activated the Hippo signalling pathway. STK4 silencing was observed to promote the proliferation ability of TC cells, inhibit the apoptosis and autophagy abilities, as well as enhance the tumorigenicity and tumour growth. Moreover, the in vitro proliferation ability as well as the in vivo tumorigenicity and tumour growth of TC cells were inhibited after the blockade of Hippo signalling pathway, while the apoptosis and autophagy abilities were promoted. The results demonstrate that the lncRNA TNRC6C‐AS1 increases STK4 promoter methylation to down‐regulate STK4 expression, thereby promoting the development of TC through activation of Hippo signalling pathway. It highlights that lncRNA TNRC6C‐AS1 may be a novel therapeutic target for the treatment of TC.

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Mapping the STK4/Hippo signaling network in prostate cancer cell

Cited by 25 publications

References 60 publications

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Hsa_Circ_0001206 is downregulated and inhibits cell proliferation, migration and invasion in prostate cancer

Suppression of long non‐coding RNA TNRC6C‐AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway

Long non‐coding RNA TNRC6C‐AS1 promotes methylation of STK4 to inhibit thyroid carcinoma cell apoptosis and autophagy via Hippo signalling pathway

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