Prognostic Impact of Bcl-2 Depends on Tumor Histology and Expression of MALAT-1 lncRNA in Non–Small-Cell Lung Cancer

Schmidt, L. H.; Görlich, Dennis; Spieker, Tilmann; Rohde, Christian; Schüler, Martin; Möhr, Michael; Humberg, Julia; Sauer, Tim; Thoenissen, Nils H.; Huge, Andreas; Voss, Reinhard; Marra, Alessandro; Faldum, Andreas; Müller‐Tidow, Carsten; Berdel, Wolfgang E.; Wiewrodt, Rainer

doi:10.1097/jto.0000000000000243

Cited by 59 publications

(41 citation statements)

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“…Some lncRNAs, for instance, PCAT1, PCGEM1, MALAT1, are reported to be potential therapeutic targets for PCa . In this study, we first found that TMPO‐AS1 was up‐regulated in PCa samples and was regulated by AR.…”

Section: Discussionmentioning

confidence: 99%

“…Long non‐coding RNAs (lncRNAs), transcripts longer than 200 nucleotides without protein translation, have been observed to function in carcinogenesis . Some can work as clinically relevant biomarkers since being linked to prognosis . Recent researches have suggested lncRNAs related to AR signaling pathways and played functions in the PCa progression .…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of AR‐regulated lncRNA TMPO‐AS1 correlates with tumor progression and poor prognosis in prostate cancer

Huang

Wang

et al. 2018

The Prostate

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overexpression of AR‐regulated lncRNA TMPO‐AS1 correlates with tumor progression and poor prognosis in prostate cancer

Huang

Wang

et al. 2018

The Prostate

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“…In NSCLC, Bcl-2, Bcl-xl and Mcl-1 are often found to be upregulated, which is associated with chemotherapy resistance and metastasis of cancers [11, 12]. These findings indicate that suppression of the anti-apoptotic Bcl-2 proteins may be a promising strategy for cancer therapy and potentially overcome the resistance to conventional chemotherapy.…”

Section: Introductionmentioning

confidence: 98%

Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells

Kang

Zhang

Qing-qin

et al. 2017

Cell Physiol Biochem

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Background/Aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis.

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“…On the other hand, in gastric cancer [12] and cutaneous Merkel cell carcinoma [13], Bax expression is obviously increased, while which decrease in colorectal cancer [14] and nasopharyngeal carcinoma [15]. As reported in nonsmall cell lung cancer [16], patients with Bcl-2 overexpression have poor clinical prognosis. In oral squamous cell carcinoma [17], patients with Bax-positive expression have a better prognosis.…”

Section: Introductionmentioning

confidence: 89%

Gas6/Axl Inhibits Osteosarcoma Apoptosis through Regulation of Apoptosis-Related Protein Bcl-2

Jiang¹,

Lai²

2016

J Bioanal Biomed

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Background: Dysregulation of the receptor tyrosine kinase Axl and its ligand Gas6 has been shown to promote the progression of osteosarcoma and correlates with poor prognosis. This study aimed to identify the role of Gas6/ Axl for anti-apoptosis as induced by cisplatin (DDP) and methotrexate (MTX) chemotherapy and to analyze the relationship between P-Axl and apoptosis-related proteins in osteosarcoma.Method: Cultured osteosarcoma cell lines MG63, 143B and U2OS were used for apoptosis assays, Axl siRNA transfection, cytotoxicity assays, cell cycle analysis, and other assessment methods. A total of 41 cases of osteosarcoma patients were included for immunohistochemistry staining and clinicopathological relative analysis. TUNEL assay was performed in ten pair's cases for apoptosis detection and relative analysis of P-Axl.Results: Among the osteosarcoma cell lines, Gas6 could obviously protect tumor cells from apoptosis induced by DDP and MTX by binding to Axl (P<0.05). Axl siRNA transfection enhanced cell apoptosis, whereas Gas6 was unable to function upon previous knockdown of Axl. Among the 41 osteosarcoma cases, the positive rate of Bcl-2, Bax, and P-Axl was 70.7%, 36.6%, and 85.4%, respectively. In osteofibrous dysplasia, the positive rate of them was 22.2%, 11.1%, and 14.6%, respectively. The expression levels of these apoptosis-related factors were significantly higher in osteosarcoma than in osteofibrous dysplasia (P<0.05). Through clinico-pathological analysis, there were significant relationships between the survival status and Bcl-2 or Bax expression (P<0.05). TUNEL assay also demonstrated that P-Axl high expression inhibited apoptosis in osteosarcoma tissues. By Cox univariate analysis, Bcl-2 or Bax was correlated with the patients' prognosis. Importantly, Pearson correlation analysis demonstrated that Bcl-2 was positively correlated to P-Axl with statistical significance (r=0.842, P<0.0001). Conclusion:Gas6/Axl protects osteosarcoma cells from the apoptosis induced by DDP and MTX chemotherapy and inhibits apoptosis in osteosarcoma tissue, possibly through the regulation of apoptosis-related protein Bcl-2. Bcl-2 was also been proved to be higly expressed in osteosarcoma, but the prognostic or predictive function of Bcl-2 or Bax in osteosarcoma were still uncertain [18], a recent meta-analysis even suggested that the bcl-2 expression might be independent with the prognosis for patients with osteosarcoma [19]. Gas6/Axl InhibitsAs we have proven, osteosarcoma cells show increased levels of activated Axl which are correlated with clinical prognosis. In this setting, Axl protects tumor cells from apoptosis and promotes their invasion and migration, potentially contributing to lung metastasis. Phosphorylated Axl may mediate these effects through Akt signaling and the up regulation of matrix metalloproteinase 9 (MMP-9) [20]. However, studies on the exact inhibition of apoptosis by Axl and the anti-apoptotic mechanisms in osteosarcoma have been rarely reported [21]. ES Papadakis et al. have confirmed th...

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Prognostic Impact of Bcl-2 Depends on Tumor Histology and Expression of MALAT-1 lncRNA in Non–Small-Cell Lung Cancer

Abstract: Bcl-2 expression was specifically associated with superior prognosis in localized NSCLC. An interaction of Bcl-2 with MALAT-1 lncRNA expression was revealed, which merits further investigation for risk prediction in resectable NSCLC patients.

Cited by 59 publications

References 46 publications

Overexpression of AR‐regulated lncRNA TMPO‐AS1 correlates with tumor progression and poor prognosis in prostate cancer

Overexpression of AR‐regulated lncRNA TMPO‐AS1 correlates with tumor progression and poor prognosis in prostate cancer

Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells

Gas6/Axl Inhibits Osteosarcoma Apoptosis through Regulation of Apoptosis-Related Protein Bcl-2

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