A regulatory loop involving miR-29c and Sp1 elevates the TGF-β1 mediated epithelial-to-mesenchymal transition in lung cancer

Zhang, Hai-wei; Wang, Enwen; Li, Lixian; Yi, Shouhui; Li, Luchun; Xu, Fen; Wang, Donglin; Wu, Yongzhong; Nian, Weiqi

doi:10.18632/oncotarget.13137

Cited by 41 publications

(39 citation statements)

References 20 publications

(24 reference statements)

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“…SP1 is a nuclear transcription factor that plays an important regulatory role in mammalian gene expression. SP1 affects the growth and metastasis of tumors by regulating the expressions of tumor‐related genes . It can bind to specific sites on the promoter of vascular endothelial growth factor (VEGF) or VEGF receptor, which further promotes the progress of tumors .…”

Section: Discussionmentioning

confidence: 99%

“…SP1 affects the growth and metastasis of tumors by regulating the expressions of tumor-related genes. [26][27][28] It can bind to specific sites on the promoter of vascular endothelial growth factor (VEGF) or VEGF receptor, which further promotes the progress of tumors. 29 SP1-regulated tumor-related genes are involved in a variety of cell functions, including cell cycle (Cyclin D1, TGF-α, E2F1), 30,31 apoptosis (Bax, Bcl2), 32,33 tumor metastasis (TGF-β, MMP2) 34 and angiogenesis (VEGF).…”

Section: Discussionmentioning

confidence: 99%

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Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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Syncytin 1 is considered as an oncogene in various malignant tumors, but its effect on non‐small cell lung cancer (NSCLC) has not been reported. We investigated the specific role of Syncytin 1 on NSCLC through the transfection of Syncytin 1 knockdown or overexpression plamids in A549 cells. Our results proved that knockdown of Syncytin 1 inhibited the proliferation, and blocked the cell cycle on G1 phase by inhibiting the expression of Nusap1, Cyclin D1, CDK6, and CDK4. Cell cycle arrest also leaded to increased apoptosis in Syncytin 1 knockdown cells. Suppression of Syncytin 1 inhibited the migration and invasion, as well as the expressions of epithelial‐mesenchymal transition (EMT) makers, N‐cadherin, β‐catenin, and Vimentin, indicating that Syncytin 1 knockdown inhibited the metastasis via reversing the EMT process in A549 cells. The phosphorylation levels of Akt, mTOR, and Erk1/2 were all decreased in Syncytin 1 knockdown cells, suggesting the signaling pathways by which Syncytin 1 operated as an oncogene in NSCLC. Moreover, the underexpression of transcription factor SP1 downregulated the Syncytin 1 expression in A549 cells. The rescue experiment of Syncytin 1 in SP1 knockdown cells further proved that Syncytin 1 could block the inhibition of cell growth induced by SP1 knockdown. In conclusion, knockdown of SP1/Syncytin1 axis inhibited the progression of NSCLC by the reversion of tumor epithelial‐mesenchymal transition process and suppression of Akt and Erk signaling pathways, suggesting that they are potential targets for targeted therapy of NSCLC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Xia

et al. 2019

Cancer Medicine

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“…A study by Zhang et al proposes a mechanism of action for miR-29c in non-small cell lung cancer. Their data suggests that miR-29c directly represses specificity protein1 (Sp1), a key protein involved in TGF-β-mediated epithelial-tomesenchymal transition (EMT) and cell invasion [34]. The theory that miR-125a functions as a tumor suppressor is supported by data from Tang et al, who transfected miR-125a mimics into human hepatocellular carcinoma (HCC) cell lines and demonstrated that colony formation and migration rates were decreased in miR-125a upregulated cells.…”

Section: Discussionmentioning

confidence: 98%

A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection

et al. 2020

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Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR (p = 0.001) and worse OS (p = 0.034). Two-year OS rates for the high-and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR (p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate (p = 0.03) and multivariable analysis (p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS (p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.

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“…Han et al (11) identified that loss of miR-29c-3p expression was an early event in the initiation of gastric carcinogenesis. Other studies have revealed that miR-29c-3p was associated with lung cancer (12), nasopharyngeal carcinoma (13), acute myeloid leukemia (14) and breast cancer (15).…”

Section: Introductionmentioning

confidence: 97%

Akt3 is a target of miR-29c-3p and serves an important function in the pathogenesis of congenital heart disease

Chen

et al. 2018

Int J Mol Med

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Our previous studies identified that the expression of microRNA-29c (miR-29c-3p) was significantly increased in the serum of pregnant women carrying fetuses with congenital heart disease (CHD) compared with in that of normal pregnant women. However, the mechanism by which miR-29c-3p affects development of the embryonic heart remained unclear. The aim of the present study was to investigate the effect and potential molecular mechanism of miR-29c-3p overexpression on P19 cell proliferation, apoptosis and differentiation. miR-29c-3p-overexpression and protein kinase Bγ (Akt3)-knockdown cell lines were constructed using transfection technology. The function of miR-29c-3p and Akt3 in cardiomyocyte development was investigated by determining the proliferation, apoptosis and differentiation of P19 cells, which can differentiate into cardiomyocytes induced by dimethylsulfoxide. Bioinformatic analysis and luciferase assays were performed to explore the association between Akt3 and miR-29c-3p. The results of the present study revealed that miR-29c-3p overexpression and Akt3 knockdown suppressed proliferation, and promoted apoptosis and differentiation in P19 cells. Akt3 was also demonstrated to be a target of miR-29c-3p. Therefore, overexpression of miR-29c-3p may inhibit proliferation, and promote apoptosis and differentiation in P19 cells by inhibiting the expression of Akt3. miR-29c-3p may be a potential therapeutic target for the treatment of CHD.

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A regulatory loop involving miR-29c and Sp1 elevates the TGF-β1 mediated epithelial-to-mesenchymal transition in lung cancer

Cited by 41 publications

References 20 publications

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

Knockdown of SP1/Syncytin1 axis inhibits the proliferation and metastasis through the AKT and ERK1/2 signaling pathways in non‐small cell lung cancer

A microRNA-based signature predicts local-regional failure and overall survival after pancreatic cancer resection

Akt3 is a target of miR-29c-3p and serves an important function in the pathogenesis of congenital heart disease

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