Sp1 transcription factor promotes <i><scp>TMEPAI</scp></i> gene expression and contributes to cell proliferation

Y, Li; A, Guo; Feng, Yingying; Zhang, Y; Wang, J; Lei, Jing; Yan, Yunjun; Z, Liu; Ma, Liwei; Diao, Aipo

doi:10.1111/cpr.12292

Cited by 15 publications

(24 citation statements)

References 35 publications

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“…Earlier data from several laboratories indicated both pro-oncogenic and tumor growth inhibitory functions of the PMEPA1 gene in various solid tumors, including cancers of the breast, lung, colon and prostate [11,14,16,19,20,[24][25][26][27][28][29][30][31][32][33][34]. Our data on distinct expressions and regulations of PMEPA1 gene isoforms (a and b) have underscored the rationale for evaluating isoform specific functions in prostate tumorigenesis and progression.…”

Section: Discussionsupporting

confidence: 56%

Analysis of PMEPA1 Isoforms (a and b) as Selective Inhibitors of Androgen and TGF-β Signaling Reveals Distinct Biological and Prognostic Features in Prostate Cancer

Sharad

Sztupinszki

Chen

et al. 2019

Cancers

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Dysfunctions of androgen/TGF-β signaling play important roles in prostate tumorigenesis. Prostate Transmembrane Protein Androgen Induced 1 (PMEPA1) inhibits androgen and TGF-β signaling via a negative feedback loop. The loss of PMEPA1 confers resistance to androgen signaling inhibitors and promotes bone metastasis. Conflicting reports on the expression and biological functions of PMEPA1 in prostate and other cancers propelled us to investigate isoform specific functions in prostate cancer (PCa). One hundred and twenty laser capture micro-dissection matched normal prostate and prostate tumor tissues were analyzed for correlations between quantitative expression of PMEPA1 isoforms and clinical outcomes with Q-RT-PCR, and further validated with a The Cancer Genome Atlas (TCGA) RNA-Seq dataset of 499 PCa. Cell proliferation was assessed with cell counting, plating efficiency and soft agar assay in androgen responsive LNCaP and TGF-β responsive PC3 cells. TGF-β signaling was measured by SMAD dual-luciferase reporter assay. Higher PMEPA1-a mRNA levels indicated biochemical recurrence (p = 0.0183) and lower PMEPA1-b expression associated with metastasis (p = 0.0173). Further, lower PMEPA1-b and a higher ratio of PMEPA1-a vs. -b were correlated to higher Gleason scores and lower progression free survival rate (p < 0.01). TGF-β-responsive PMEPA1-a promoted PCa cell growth, and androgen-responsive PMEPA1-b inhibited cancer cell proliferation. PMEPA1 isoforms -a and -b were shown to be promising candidate biomarkers indicating PCa aggressiveness including earlier biochemical relapse and lower disease specific life expectancy via interrupting androgen/TGF-β signaling.

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Section: Discussionsupporting

confidence: 56%

Analysis of PMEPA1 Isoforms (a and b) as Selective Inhibitors of Androgen and TGF-β Signaling Reveals Distinct Biological and Prognostic Features in Prostate Cancer

Sharad

Sztupinszki

Chen

et al. 2019

Cancers

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“…Sp1 is a well‐known transcription regulator that binds specifically to GC‐box elements in the promoter region of target genes . Since identification, the oncogenic effects of Sp1 on cancer progression, including cell proliferation and EMT‐related metastasis, have been widely elucidated . However, the question of whether Sp1 is an oncogene has generated controversy, as much of the experimental evidence has presented the opposite opinion about Sp1, suggesting that Sp1 induced apoptosis or cooperated with tumor suppressors .…”

Section: Discussionmentioning

confidence: 99%

“…66 Since identification, the oncogenic effects of Sp1 on cancer progression, including cell proliferation and EMT-related metastasis, have been widely elucidated. [67][68][69] However, the question of whether Sp1 is an oncogene has generated controversy, as much of the experimental evidence has presented the opposite opinion about Sp1, suggesting that Sp1 induced apoptosis or cooperated with tumor suppressors. 70,71 A decade ago, a novel concept was established that cancer was dependent on genes for tumor formation and maintenance in terms of "oncogene addiction" (OA) and "nononcogene addiction" (NOA).…”

Section: Sp1 Plays a Crucial Role In Dmba-induced Signalingmentioning

confidence: 99%

7,12‐Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β‐catenin signaling and EMT process

Kwon

Baek

et al. 2018

Environmental Toxicology

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7,12-Dimethylbenz[α]anthracene (DMBA) is a hazardous component present in polluted environments. DMBA has been used as an experimental tool for in vivo tumor formation owing to its carcinogenic effects, but the detailed molecular mechanism of DMBA has not been fully established. To comprehend the carcinogenic mechanism of DMBA, we explored its effects in the breast cancer cell lines, MCF-7 and MDA-MB-231, and the cervical cancer cell line, HeLa. Cell viability assay and measurement of a proliferation marker showed that DMBA markedly increased cancer cell proliferation. Furthermore, morphological observations and wound healing assays in nontumorigenic MCF-10A cells and trans-well invasion assays in cancer cells following DMBA treatment revealed that DMBA induced cell migration and invasion. To reveal the molecular mechanism of DMBA, we investigated the effects of DMBA on the epithelial-mesenchymal transition (EMT) process and Wnt/β-catenin signaling, a critical pathway for cell proliferation that was reported to correlate with the EMT process, by using quantitative RT-PCR (qPCR), western blot analysis, and confocal microscopy. Consequently, we found that DMBA increased cancer cell proliferation and invasion through the promotion of EMT-inducing factors and β-catenin. Especially, it was revealed in promoter activity assay using mutated luciferase vectors on transcription factor-binding sites that TWIST1 is promoted by DMBA through induction of STAT3-mediated promoter activation. To further elucidate the detailed mechanism of DMBA, we aimed to identify the key regulator of its carcinogenic action. DMBA was shown to significantly upregulate the expression of specificity protein 1 (Sp1), a transcription factor, and the carcinogenic effects of DMBA were blocked via the suppression or interruption of Sp1 activity. In conclusion, our data suggested that DMBA induced carcinogenic effects through activation of Wnt/β-catenin signaling and the EMT process by upregulating Sp1 activity.

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“…Specific protein‐1 (SP1) is a member of the specificity protein/Kruppel‐like factor family that contributes to the regulation of cell growth and apoptosis . Yao et al suggest that SP1 is highly expressed in PD model, and its inhibition can display neuroprotective effects through inactivating monoamine oxidase B (MAO B) .…”

Section: Introductionmentioning

confidence: 99%

MiR‐29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1

Wang

Yang

Wang

et al. 2019

Clin Exp Pharma Physio

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MicroRNAs (miRNAs) have been shown to have complicated implications in the pathogenesis of Parkinson's disease (PD). However, the role of miR‐29c and the underlying mechanism in the development of PD remain not well understood. In this work, the MPTP‐treated mice or MPP+‐intoxicated SH‐SY5Y cells were established as an in vivo or in vitro PD model. Then the specific agomir of miR‐29c was employed to examine its biological function on PD progress. We found that miR‐29c was down‐expressed but SP1 was high‐expressed in substantia nigra pars compacta (SNpc) of MPTP‐induced PD mice. Overexpression of miR‐29c attenuated dopaminergic neuron loss and α‐synuclein accumulation in SNpc of PD mice. Furthermore, the increments of pro‐inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) and TUNEL‐positive apoptotic cells in MPTP‐treated mice were ameliorated by miR‐29c. Similarly, in SH‐SY5Y cell models of PD, we also found that miR‐29c inhibited inflammatory cytokine production, reduced apoptotic rate and suppressed pro‐apoptotic regulator activity. In addition, the increased expression of SP1 in PD models was found to be inhibited by miR‐29c. Luciferase reporter assay confirmed that SP1 was complementary with miR‐29c. Knockdown of SP1 with siRNA restored α‐synuclein accumulation, inflammation and apoptosis in MPP+‐induced SH‐SY5Y cells. Collectively, this current work presents that miR‐29c may directly target SP1 to protect against the neuroinflammatory and apoptotic responses in PD, providing a potential biomarker for PD diagnosis and treatment.

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Sp1 transcription factor promotes TMEPAI gene expression and contributes to cell proliferation

Abstract: These results indicate that the sequence between -298 and +24 consists of the basal promoter activity for TMEPAI. Sp1 promotes TMEPAI expression and contributes to cell proliferation.

Cited by 15 publications

References 35 publications

Analysis of PMEPA1 Isoforms (a and b) as Selective Inhibitors of Androgen and TGF-β Signaling Reveals Distinct Biological and Prognostic Features in Prostate Cancer

Analysis of PMEPA1 Isoforms (a and b) as Selective Inhibitors of Androgen and TGF-β Signaling Reveals Distinct Biological and Prognostic Features in Prostate Cancer

7,12‐Dimethylbenz[α]anthracene increases cell proliferation and invasion through induction of Wnt/β‐catenin signaling and EMT process

MiR‐29c protects against inflammation and apoptosis in Parkinson's disease model in vivo and in vitro by targeting SP1

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