Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC

Zhou, Maojun; Zhang, Qi; Zhao, Jinfeng; Liao, Mingmei; Wen, Sailan; Yang, Manyi

doi:10.3892/or.2017.5830

Cited by 33 publications

(29 citation statements)

References 54 publications

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“…8). Regarding the undetectable Bcl-2 expression in the Huh-7 cells, Wang et al (34) reported a similar result; however certain studies have detected it, but reported that it was lower in Huh-7 cells compared with other hepatoma cell lines (35,36). There is a possibility that the expression of Bcl-2 was not detected in the present study due to different experimental conditions.…”

Section: Discussionsupporting

confidence: 59%

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

et al. 2019

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Protein disulfide-isomerase A3 (PDIA3) is a chaperone protein that modulates folding of newly synthesized glycoproteins and responds to endoplasmic reticulum (ER) stress. Previous studies reported that increased expression of PDIA3 in hepatocellular carcinoma (HCC) is a marker for poor prognosis. However, the mechanism remains poorly understood. The aim of the present study, therefore, was to understand the role of PDIA3 in HCC development. First, immunohistochemical staining of tissues from 53 HCC cases revealed that HCC tissues with high PDIA3 expression exhibited a higher proliferation index and contained fewer apoptotic cells than those with low expression. In addition, the knockdown of PDIA3 significantly inhibited cell proliferation and induced apoptosis in HCC cell lines. These results suggest that PDIA3 regulates cell proliferation and apoptosis in HCC. An examination of whether PDIA3 knockdown induced apoptosis through ER stress revealed that PDIA3 knockdown did not increase ER stress marker, 78 kDa glucose-regulated protein, in HCC cell lines. Furthermore, the association between PDIA3 and the signal transducer and activator of transcription 3 (STAT3) signaling pathway were investigated in vitro and in vivo. Immunofluorescence staining and co-immunoprecipitation experiments revealed colocalization and binding, respectively, of PDIA3 and STAT3 in HCC cell lines. The knockdown of PDIA3 decreased the levels of phosphorylated STAT3 (P-STAT3; Tyr705) and downstream proteins of the STAT3 signaling pathway: The anti-apoptotic proteins (Bcl-2-like protein 1, induced myeloid leukemia cell differentiation protein Mcl-1, survivin and X-linked inhibitor of apoptosis protein). In addition, PDIA3 knockdown provided little inhibitory effect on cell proliferation in HCC cell lines treated with AG490, a tyrosine-protein kinase JAK/STAT3 signaling inhibitor. Finally, an association was demonstrated between PDIA3 and P-STAT3 expression following immunostaining of 35 HCC samples. Together, the present data suggest that PDIA3 promotes HCC progression through the STAT3 signaling pathway.

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Section: Discussionsupporting

confidence: 59%

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

et al. 2019

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“…However, the way of ICT1 regulating BCL-2 is unknown. The previous studies reported that BCL-2 is an anti-apototic molecule, which is phosphorylated at Ser70 by growth factor-activated protein kinases including PKC and the MAPKs (ERK1/2) can actively control the anti-apoptotic function of BCL-2 [28][29][30]. It is unclear that wheather ICT1 leads to phosphoylation of BCL-2 to inhibit apoptosis.…”

Section: Discussionmentioning

confidence: 99%

ICT1 Knockdown inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2

Pan

Tan

et al. 2020

Preprint

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Background:Osteosarcoma (OS) which occurs mainly in the young people is a familiar malignant bone tumor. Apoptosis is a kind of programmed and managed cell death and promoting apoptosis of OS cells is an important treatment for OS. However, the pathways of controlling apoptosis in OS remain unclear. Immature colon carcinoma transcript-1 (ICT1) belongs to a family of four putative mitochondrial translation release factors. It controls the termination stage of translation. Methods:In this study, the function of ICT1 was elucidated by a series of in vivo and in vitro assays. The potential downstream targets of ICT1 in the OS was confirmed by Quantitative real‑time polymerase chain reaction (qRT-PCR) and western blotting, while immunohistochemical analysis and rescue experiment were performed to confirm this result. Results: ICT1 was significantly upregulated in osteosarcoma, and higher expression of ICT1 led to the worse survival rate. Furthermore, knockdown of ICT1 could inhibit the cell proliferation, but improved the apoptosis of cells in vitro and in vivo. In addition, our data demonstrated that BCL-2, apoptotic related-genes, is a potential target of ICT1 and the overexpression of BCL-2 partly reduced the negative influence of ICT1 knockdown on the pro-tumorigenic capabilities of OS cells in vitro. Conclusion: The ICT1 protein was overexpressed in the OS and has identified a novel mechanism by which ICT1 inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2.

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“…After treatment, the cells were harvested and the whole-cell extracts were prepared as the method previously described [26]. Protein concentration was measured according to the BAC Assay Reagent.…”

Section: Cell Extraction and Western Blottingmentioning

confidence: 99%

“…Protein concentration was measured according to the BAC Assay Reagent. Western blot was performed as the protocol described before [26].…”

Section: Cell Extraction and Western Blottingmentioning

confidence: 99%

“…Immunofluorescence H1299 cells were seeded on coverslips in a 24-well plate. After transfected by at least 24h, cells were fixed and immofluorescence was done as previously described [26]. After fixed for 15min in 4% formaldehyde solution, cells were washed three times in PBST (0.05% Tween-20 in PBS) and then blocked with 5% BSA in PBST at room temperature for 1h.…”

Section: Cell Extraction and Western Blottingmentioning

confidence: 99%

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Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells

Zhou¹,

Zhao²,

Zhang³

et al. 2020

J. Cancer

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Background: Nicotine contributes to development of human lung cancer and chemoresistance through activation of myeloid cell leukemia-1 (Mcl-1). Signal transducer and activator of transcription 3 (STAT3) generally participates in development and progression of human cancers. Therefore, we examined the STAT3 cascade in nicotine regulation of Mcl-1 transcription in human lung cancer cells. Methods: The effects of nicotine on the expression of STAT3 and Mcl-1 were determined using western blot. The sub-cellular localization was tested using immunofluorescence. The activity of STAT3 promoter was checked using dual luciferase reporter assay. Results: STAT3 was constitutively activated (i.e., tyrosine-phosphorylated, serine-phosphorylated and nuclear translocation), meanwhile the expression and transcriptional activity of Mcl-1 were up-regulated in lung cancer cells following treatment with nicotine. Transfection with siRNA targeting STAT3 or treatment with STAT3 inhibitor JSI-124 diminished Mcl-1 protein levels. Deleted mutagenesis of a putative STAT3 consensus binding sequence decreased Mcl-1 promoter activity and eliminated the increase of Mcl-1 promoter activity induced by nicotine. Abnormally, JAK (Jannus kinase) inhibitor AG490 can't induce the downregulation of Mcl-1 or inhibit the tyrosine-phosphorylation of STAT3. In addition, deactivated mutagenesis of STAT3 the tyrosine 705 site had no effect on the aggregation of STAT3 into nucleus induced by nicotine. Conclusions:We have demonstrated that nicotine induces up-regulation of Mcl-1 through STAT3, which process may be independent on JAKs and not only dependent on the phosphorylation of Y705. Downregulation of Mcl-1 transcription by inhibiting STAT3 cascade may be a potential strategy for the treatment of this cancer.

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Phosphorylation of Bcl-2 plays an important role in glycochenodeoxycholate-induced survival and chemoresistance in HCC

Cited by 33 publications

References 54 publications

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

Downregulation of protein disulfide‑isomerase A3 expression inhibits cell proliferation and induces apoptosis through STAT3 signaling in hepatocellular carcinoma

ICT1 Knockdown inhibits osteosarcoma cell proliferation by regulating cell apoptosis through targeting BCL-2

Nicotine Upregulates the Level of Mcl-1 through STAT3 in H1299 Cells

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