STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway

Han, Yidi; Chen, Meizhu; Wang, Aili; Fan, Xiaoping

doi:10.1016/j.bbrc.2018.11.092

Cited by 51 publications

(33 citation statements)

References 28 publications

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“…Concordant with our results, PTEN has been proposed as a promising biomarker of the tumor grade and disease stage in patients with HCC considering its role in counterbalancing apoptosis and proliferation [18]. Besides, accumulating evidences have suggested the participation of the activated PI3K/Akt pathway in the growth-promoting effects of PTEN in HCC [19][20][21][22].…”

Section: Discussionsupporting

confidence: 89%

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

et al. 2020

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Background: Metabolic reprogramming, in which energetic metabolism changes from oxidative phosphorylation to glycolysis, is well-accepted as a hallmark of cancers including hepatocellular carcinoma (HCC). A growing body of evidence suggests the involvement of oncogenes and tumor suppressor genes in the control of metabolic reprogramming. In this study, we attempt to investigate whether loss of PTEN, a recognized tumor suppressor, drives metabolic reprogramming of HCC. Methods: Cancerous liver tissues were surgically resected from 128 HCC patients, with 43 adjacent noncancerous liver tissues as control. Aerobic glycolysis (Warburg effect) was reflected by measurements of glucose uptake and lactate production, mitochondrial membrane potential collapse was observed by JC-1 staining, glycolytic rate and mitochondrial respiration were evaluated by determining glycolytic proton efflux rate (glycoPER) and oxygen consumption rate (OCR) in cultured human HHCC cells. Results: Reciprocal expression of PTEN and PI3K was determined in cancer liver tissues. Overexpression of PTEN suppressed the Warburg effect, as evidenced by reductions in glucose uptake and lactate production, maintenance of mitochondrial function, and transformation of energetic metabolism from glycolysis to oxidative phosphorylation in cultured PTEN-negative HHCC cells. Importantly, 740 Y-P, a PI3K agonist that leads to activation of the PI3K pathway, partially abrogated the function of PTEN and reprogramed glucose metabolism in cultured HHCC cells. Conclusions: The discovery that loss of PTEN allows the tumor metabolic program has been a major advance in understanding the carcinogenesis of HCC.

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Section: Discussionsupporting

confidence: 89%

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

et al. 2020

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“…PTEN is a tumor suppressor gene, which could negatively regulate the Akt/GSK-3β/β-catenin pathway (42). In addition, PTEN could regulate proliferation, migration and invasion of HCC (43,44). Moreover, Wan et al (45) showed that miR-25-3p promoted malignant phenotypes of retinoblastoma by targeting PTEN and activating Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane inhibits the proliferation and invasion of hepatocellular carcinoma cells through regulating the PTEN/Akt/GSK‑3β/β‑catenin signaling pathway by downregulating miR‑25‑3p

Cao

Ding

et al. 2020

Int J Mol Med

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Sevoflurane (Sevo) is one of the most frequently used volatile anesthetic agents in surgical oncology and has various effects on tumors, including inhibiting tumor growth, recurrence, and metastases; however, the molecular mechanisms are unknown. This study tried to investigate the influence of Sevo on hepatocellular carcinoma (HCC) cells and its possible mechanisms of action. The present study found that Sevo suppressed both the proliferative and invasive capabilities of both HCCLM3 and Huh7 cells in a dose-dependent manner. Moreover, 53 differentially expressed microRNAs (miRNAs/miRs) in HCC cells that resulted from Sevo were screened out using miRNA microarray assay. In particular, miR-25-3p displayed a significant decrease in response to Sevo treatment. Further studies showed that Sevo's inhibitory actions on HCC cells were attenuated by overexpression of miR-25-3p but enhanced by its inhibitor. Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN (PTEN), a tumor suppressor gene, was directly targeted by miR-25-3p and its expression was upregulated by Sevo. In addition, Sevo suppressed the expression of phosphorylated-protein kinase B (p-Akt) (S473), glycogen synthase kinase (GSK) 3β (p-GSK3β) (S9), β-catenin, c-Myc and matrix metalloproteinase 9; whereas these inhibitory effects were reversed by miR-25-3p overexpression. More importantly, Sevo's tumor-suppressive effects were enhanced by LY294002 (a PI3-kinase inhibitor) but weakened by insulin growth factor-1 (an agonist of the Akt signaling pathway). These data suggest that Sevo's antitumor effects on HCC could be explained, in part, by Sevo inhibiting the miR-25-3p/PTEN/Akt/GSK-3β/β-catenin signaling pathway.

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“…EZH2 epigenetically suppressed gene expression through increasing H3K27me3 . PTEN was reported to be suppressed by lncRNAs, through recruiting EZH2 and subsequently increasing H3K27me3 level . Therefore, we further explored whether PCAT‐1 regulated PTEN expression through binding with EZH2.…”

Section: Discussionmentioning

confidence: 99%

PCAT‐1 contributes to cisplatin resistance in gastric cancer through epigenetically silencing PTEN via recruiting EZH2

Yang

et al. 2019

J of Cellular Biochemistry

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The aim of this study was to investigate the functional role and the underlying molecular mechanism of long noncoding RNA (lncRNA) prostate cancer–associated transcript 1 (PCAT‐1) in cisplatin resistance of gastric cancer (GC). Our results indicated that PCAT‐1 was overexpressed in CDDP‐resistant GC tumor tissues and cell lines. High expression of PCAT‐1 was closely correlated with short overall survival in patients with GC. Downregulation of PCAT‐1 resensitized CDDP‐resistant GC cells to cisplatin. In addition, PCAT‐1 epigenetically silenced PTEN through binding to the histone methyltransferase enhancer of zeste homolog 2 (EZH2), thus increasing H3K27me3. More importantly, PTEN silencing counteracted PCAT‐1 knockdown–mediated enhancement in cisplatin sensitivity of CDDP‐resistant GC cells. In summary, PCAT‐1 led to cisplatin resistance in GC cells through epigenetically suppressing PTEN expression, providing a novel therapeutic strategy for GC patients with chemoresistance.

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STAT3-induced upregulation of lncRNA CASC11 promotes the cell migration, invasion and epithelial-mesenchymal transition in hepatocellular carcinoma by epigenetically silencing PTEN and activating PI3K/AKT signaling pathway

Cited by 51 publications

References 28 publications

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

Loss of PTEN expression is associated with PI3K pathway-dependent metabolic reprogramming in hepatocellular carcinoma

Sevoflurane inhibits the proliferation and invasion of hepatocellular carcinoma cells through regulating the PTEN/Akt/GSK‑3β/β‑catenin signaling pathway by downregulating miR‑25‑3p

PCAT‐1 contributes to cisplatin resistance in gastric cancer through epigenetically silencing PTEN via recruiting EZH2

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