Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway

Jia, Kaiqi; Sun, Da; Ling, Sunbin; Tian, Yu; Yang, Xuejun; Sui, Jidong; Tang, Bo; Wang, Liming

doi:10.3892/mmr.2014.2301

Cited by 20 publications

(16 citation statements)

References 34 publications

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“…DOR activation inhibits serum deprivation-induced apoptosis via the activation of PKC and the mitochondrial pathway in human liver cells [63]. DOR activation inhibited mitochondria-mediated apoptosis in liver cancer cells through the PKC/ERK signaling pathway [64], which is consistent with the observation made in neuronal cells [60, 62]. Apparently, DOR actively participates in the regulation of hepatic cell survival.…”

Section: Discussionsupporting

confidence: 66%

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O₂) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.

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Section: Discussionsupporting

confidence: 66%

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Zhi

Shao

Xue

et al. 2017

Cell Physiol Biochem

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“…The SMAC-mediated mitochondrial apoptotic pathway plays a key regulatory role in the development and progression of malignancies such as breast cancer [27], prostate cancer [28], and liver cancer [29]. Our study showed that downregulation of HSF1 promotes both SMAC expression and apoptosis in pancreatic cancer cells.…”

Section: Discussionmentioning

confidence: 75%

Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis

Liang

Liao

Zhang

et al. 2017

J Exp Clin Cancer Res

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BackgroundAs a relatively conservative transcriptional regulator in biological evolution, heat shock factor 1 (HSF1) is activated by, and regulates the expression of heat shock proteins (HSPs) in response to a variety of stress conditions. HSF1 also plays a key role in regulating the development of various tumors; however, its role in pancreatic cancer and the specific underlying mechanism are not clear.MethodsWe first examined HSF1 expression in pancreatic cancer tissues by immunohistochemistry, and then studied its clinical significance. We then constructed HSF1-siRNA to investigate the potential of HSF1 to regulate apoptosis, proliferation and the cell cycle of pancreatic cancer cells and the underlying mechanism both in vitro and in vivo. Protein chip analysis was used subsequently to explore the molecular regulation pathway. Finally, second mitochondria-derived activator of caspase (SMAC)-siRNA was used to validate the signaling pathway.ResultsHSF1 was highly expressed in pancreatic cancer tissues and the level of upregulation was found to be closely related to the degree of pancreatic cancer differentiation and poor prognosis. After HSF1-silencing, we found that pancreatic cancer cell proliferation decreased both in vitro and in vivo and the apoptotic cell ratio increased, while the mitochondrial membrane potential decreased, and the cells were arrested at the G0/G1 phase. In terms of the molecular mechanism, we confirmed that HSF1 regulated SMAC to inhibit mitochondrial apoptosis in pancreatic cancer cells, and to promote the occurrence of pancreatic tumors. SMAC silencing reversed the effects of HSF1 silencing.ConclusionOur study provides evidence that HSF1 functions as a novel oncogene in pancreatic tumors and is implicated as a target for the diagnosis and treatment of pancreatic cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-017-0537-x) contains supplementary material, which is available to authorized users.

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“…However, we were unable to detect the altered BCL-xL expression in HCC after modulating Pinin expression (data not shown), indicating that other molecules or signaling pathways may contribute to Pinin's effects. Indeed, the phosphorylation status of ERK1/2 that are key molecules in MAPK pathway and well known for the growth promotion and anti-apoptotic effects in HCC, was associated with Pinin expression in GD treated HCC cells [27]. It was clear that ERK activation gradually disappeared with GD treatment in 24 h. However, in Pinin depleted cells this effect was further accelerated as it was shown that ERK phosphorylation reduced more rapidly at 12 h after GD treatment.…”

Section: Discussionmentioning

confidence: 99%

Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis

et al. 2016

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The roles of Pinin have been well studied in epithelial cell-cell adhesion and RNA alternative splicing, which suggests its involvement in cancer progression. However, little is known about the association between Pinin expression and hepatocellular carcinoma (HCC) tumorigenesis. In this study we report increased expression of Pinin in HCC tissues and cells. Elevated levels of Pinin closely associates with pathological grade and overall survival of patients with hepatocellular carcinoma. Suppression of Pinin expression via lentivirus mediated shRNA knockdown inhibits HCC cell proliferation, colony formation, cell viability, but promotes glucose deprivation (GD)-induced cell apoptosis. On the contrary, overexpression of Pinin reverses these effects observed in Pinin depleted cells. Meanwhile, overexpression of Pinin attenuates GD initiated poly ADP-ribose polymerase (PARP) cleavage and ERK1/2 dephosphorylation, which can be completely blocked with MEK1/2 inhibitor U0126. Therefore, we conclude that Pinin contributes to HCC progression and resistance to GD-induced apoptosis via maintaining ERK1/2 activation and hence may be a potential therapeutic target in hepatocellular carcinoma treatment.

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Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway

Cited by 20 publications

References 34 publications

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

Heat shock factor 1 inhibits the mitochondrial apoptosis pathway by regulating second mitochondria-derived activator of caspase to promote pancreatic tumorigenesis

Pinin associates with prognosis of hepatocellular carcinoma through promoting cell proliferation and suppressing glucose deprivation-induced apoptosis

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