RLIP76-dependent suppression of PI3K/AKT/Bcl-2 pathway by miR-101 induces apoptosis in prostate cancer

Yang, Jing; Song, Qi; Cai, Yi; Wang, Peng; Wang, Min; Zhang, Dong

doi:10.1016/j.bbrc.2015.06.032

Cited by 30 publications

(19 citation statements)

References 22 publications

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“…Consistent with previous studies, high doses of quercetin, especially at the 100 mg/kg, in our study showed similar effects on suppression of inflammation, apoptosis and oxidative stress [19,31]. Atherosclerosis is also characterized by lipids accumulation in the coronary artery, and high fructose-induced atherosclerosis in animals has been studied before [32]. Evidence is suggested that high consumption of dietary fructose is an important contributor to metabolic syndrome that injures vascular smooth muscle cells with lipid accumulation, causing liver, heart, and kidney function loss [33,34].…”

Section: Discussionsupporting

confidence: 93%

“…Also, quercetin treatment could also enhance AKT activation after receiving LPS in the presence of AKT or/and Bcl-2 silence. PI3K/AKT has been known to regulate apoptosis via modulating Bcl-2 and Caspase-3 [32,33]. Consistently, as a signal next to AKT for apoptosis regulation, Bcl-2, an anti-apoptotic member, was also suppressed for LPS, which was further inhibited due to its knockdown, while being accelerated for quercetin ( Fig.…”

Section: Quercetin Inhibited Atherosclerosis In Lps-induced Vsmcs Linsupporting

confidence: 56%

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Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway

Zhao

Yao

et al. 2017

Biomedicine & Pharmacotherapy

109

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Section: Discussionsupporting

confidence: 93%

Section: Quercetin Inhibited Atherosclerosis In Lps-induced Vsmcs Linsupporting

confidence: 56%

Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway

Zhao

Yao

et al. 2017

Biomedicine & Pharmacotherapy

109

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“…We and others have earlier shown that reduced expression of miR-101 leads to overexpression of oncogenic histone methyltransferase EZH2 in multiple tumors. 11, 13, 36, 49 A genomic loss of miR-101 or epigenetic silencing leads to reduction in miR-101 expression in multiple cancers. 50, 51 These observations suggest that attenuation of miR-101 expression is an important event in oncogenesis.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

et al. 2016

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MicroRNA-101, a tumor suppressor microRNA is often down-regulated in cancer and is known to target multiple oncogenes. Some of the genes that are negatively regulated by miR-101 expression include histone methyltransferase EZH2, COX2, POMP, CERS6, STMN1, MCL-1 and ROCK2, among others. In the present study, we show that mir-101 targets transcriptional coactivator SUB1 homolog (Saccharomyces cerevisiae)/PC4 (positive cofactor 4) and regulates its expression. SUB1 is known to play diverse role in vital cell processes such as DNA replication, repair and heterochromatinization. SUB1 is known to modulate transcription and acts as a mediator between the upstream activators and general transcription machinery. Expression profiling in several cancers revealed SUB1 overexpression, suggesting a potential role in tumorigenesis. However, detailed regulation and function of SUB1 has not been elucidated. In this study, we show elevated expression of SUB1 in aggressive prostate cancer. Knockdown of SUB1 in prostate cancer cells resulted in reduced cell proliferation, invasion and migration in vitro, and tumor growth and metastasis in vivo. Gene expression analyses coupled with chromatin immunoprecipitation revealed that SUB1 binds to the promoter regions of several oncogenes such as polo-like kinase PLK1, C-MYC, serine threonine kinase BUB1B and regulates their expression. Additionally, we observed SUB1 down-regulated CDKN1B expression. PLK1 knockdown or use of PLK1 inhibitor can mitigate oncogenic function of SUB1 in benign prostate cancer cells. Thus, our study suggests that miR-101 loss results in increased SUB1 expression and subsequent activation of known oncogenes driving prostate cancer progression and metastasis. This study therefore demonstrates functional role of SUB1 in the prostate cancer and identifies its regulation, and potential downstream therapeutic targets of SUB1 in prostate cancer.

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“…In addition, inhibition of the PI3K-Akt pathway promotes Bax translocation to mitochondria, leading to apoptosis [40]. Inhibited RLIP76 expression can transactivate phosphorylation of PI3K-Akt signaling and result in apoptosis [41]. We next tested the functional roles of the potential signaling pathway in shikonin-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm. Tyrosine kinase inhibitors (TKIs) are commonly used to treat CML; however, drug resistance of CML cells to TKIs has limited their clinical application. Shikonin, a traditional Chinese herb, has long been used to treat leukemia in China, but the roles and related molecular mechanisms of shikonin treatment in CML remain unclear. Here, we aimed to evaluate the effects of shikonin on the proliferation, apoptosis, and migration of K562 cells, a CML cell line. Methods: Firstly, K562 cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry with Annexin V-FITC/PI staining. Cell migration was measured by Transwell migration assay. In addition, western blot was performed to determine the proteins (PI3K, Bax, Bcl-2, cleaved caspase-3, PTEN, p-AKT, AKT, CXCR4, SDF-1, CD44) involved in the mechanism of action of shikonin. Finally, neutrophils from peripheral blood of CML patients were obtained, and cell proliferation and apoptosis were tested by CCK8 assay and flow cytometry. Results: Shikonin reduced the proliferation of K562 cells in a time- and dose-dependent manner and promoted the apoptosis of K562 cells. Moreover, shikonin increased the PTEN level and inactivated the PI3K/AKT signaling pathway, subsequently upregulating BAX in K562 cells. In addition, shikonin could block K562 cell migration via the CXCR4/SDF-1 axis. Finally, shikonin significantly inhibited the proliferation and promoted the apoptosis of neutrophils from CML patients. Conclusion: These results demonstrated that shikonin inhibits CML proliferation and migration and induces apoptosis by the PTEN/PI3K/AKT pathway, revealing the effects of shikonin therapy on CML.

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RLIP76-dependent suppression of PI3K/AKT/Bcl-2 pathway by miR-101 induces apoptosis in prostate cancer

Cited by 30 publications

References 22 publications

Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway

Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway

MicroRNA-101 regulated transcriptional modulator SUB1 plays a role in prostate cancer

The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

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