HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation

Yan, Jiliang; Ma, Chunyan; Cheng, Jing; Li, Zhengguo; Liu, Chao

doi:10.3892/or.2015.4202

Cited by 33 publications

(33 citation statements)

References 34 publications

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“…Overexpression of HAX-1 inhibits mitochondria collapse and subsequent release of mitochondria-sourced apoptotic molecules (such as cytochrome c). Therefore, HAX-1 protects the cancer cells from drug-initiated apoptotic signaling [31–33]. In this study, we found that enforced expression of miR-125a promoted cisplatin-induced cell death by decreasing HAX- 1 expression directly.…”

Section: Discussionmentioning

confidence: 68%

Inhibition ofHAX-1by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

Tang

et al. 2016

Oncotarget

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Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma. Recently, studies indicate that cancer stem cells are responsible for chemotherapy failure. In addition, microRNAs play important roles in tumor initiation, development and multidrug resistance. In the present study, we found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of-function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in vitro and in vivo. Combination with microRNA-125a mimics can decrease the half maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after the cells were transfected with microRNA-125a mimics. These dates strongly suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal carcinoma.

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Section: Discussionmentioning

confidence: 68%

Inhibition ofHAX-1by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

Tang

et al. 2016

Oncotarget

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“…Upon apoptotic stimuli, some caspase-9 is discovered to move to the mitochondria and co-localized with HAX-1 [46]. Recent study also displayed that apoptosis in prostate cancer is suppressed by inhibition of caspase-9 [47]. Thus, HAX-1 is an anti-apoptotic molecule through inhibiting caspase-9 in some special cells.…”

Section: Endogenous Regulators Of Caspase-9mentioning

confidence: 99%

Caspase-9: structure, mechanisms and clinical application

et al. 2017

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As the most intensively studied initiator caspase, caspase-9 is a key player in the intrinsic or mitochondrial pathway which is involved in various stimuli, including chemotherapies, stress agents and radiation. Caspase-9 is activated on the apoptosome complex to remain catalytic status and is thought of involving homo-dimerization monomeric zymogens. Failing to activate caspase-9 has profound physiological and pathophysiological outcomes, leading to degenerative and developmental disorders even cancer. To govern the apoptotic commitment process appropriately, plenty of proteins and small molecules involved in regulating caspase-9. Therefore, this review is to summarize recent pertinent literature on the comprehensive description of the molecular events implicated in caspase-9 activation and inhibition, as well as the clinical trials in progress to give deep insight into caspase-9 for suppressing cancer. We hope that our concerns will be helpful for further clinical studies addressing the roles of caspase-9 and its regulators demanded to identify more effective solutions to overcome intrinsic apoptosis-related diseases especially cancer.

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“…Caspase-9, a protein mainly localized in mitochondria, is a critical regulatory player in mitochondria-mediated apoptosis pathway. Activated caspase-9 cleaves and activates caspase-7 and -3 directly, leading to the biochemical destruction of the cells [31]. Bax is one of the pro-apoptotic genes, the overexpression of which results in apoptosis in a number of cells [32].…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

Han

Nie

et al. 2018

Cell Physiol Biochem

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Background/Aims: Gastric cancer is considered as a common malignancy with a poor prognosis as well as unsatisfactory treatment. Neutrophil gelatinase-associated lipocalin (NGAL) has been reported to affect multiple aspects of human tumor, including gastric cancer. This study aims to explore the effects of NGAL gene silencing on the proliferation as well as apoptosis of human gastric cancer MGC-803 cells. Methods: This study included 87 patients with gastric cancer. MGC-803 cells were collected and mainly treated with siRNA against NGAL and recombinant NGAL plasmid. The expression of NGAL mRNA and the expressions of NGAL protein and apoptosis-related proteins were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Cell cycle and apoptosis were tested by flow cytometry, and cell proliferation was detected by water soluble tetrazolium-1 (WST-1) assay. The effect of NGAL gene silencing on tumorigenicity of MGC-803 cells in vivo was detected through establishment of xenograft in nude mice. Results: NGAL was highly expressed in gastric cancer tissues. The protein and mRNA expressions of NGAL gene in MGC-803 cells treated with NGAL-siRNA were obviously reduced, and the amount of cells in G0/G1 phase was increased. Moreover, MGC-803 cells treated with NGAL-siRNA exhibited inhibited proliferation, enhanced apoptosis, decreased expressions of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) as well as B-cell lymphoma-2 (Bcl-2) and increased expressions of cysteine-aspartic acid specific protease-9 (caspase-9) and Bcl2-associated X (Bax), as well as repressed tumorigenicity in vivo. Conclusion: NGAL gene silencing inhibits proliferation and promotes apoptosis of MGC-803 cells, which can provide a novel theory for treatment of gastric cancer.

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HAX-1 inhibits apoptosis in prostate cancer through the suppression of caspase-9 activation

Cited by 33 publications

References 34 publications

Inhibition ofHAX-1by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

Inhibition ofHAX-1by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells

Caspase-9: structure, mechanisms and clinical application

Downregulation of NGAL is Required for the Inhibition of Proliferation and the Promotion of Apoptosis of Human Gastric Cancer MGC-803 Cells

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