The Involvement of miR-23a/APAF1 Regulation Axis in Colorectal Cancer

Yong, Fung Lin; Wang, Chee Woon; Roslani, April Camilla; Law, Chee Wei

doi:10.3390/ijms150711713

Cited by 30 publications

(18 citation statements)

References 31 publications

(33 reference statements)

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“…Also, this study confirmed the findings of other studies on human malignancy that APAF1 expression is associated with inhibition of tumor cell apoptosis (27,31). This study also confirmed that the expression of APAF1 is associated with adverse patient prognosis (32,33).…”

Section: Discussionsupporting

confidence: 91%

“…APAF1 is closely related to several oncogenes and tumor suppressor genes, including B-cell lymphoma-2 (Bcl-2) and p53 (29,30). A series of studies have shown that APAF1 protein is an important apoptosis factor that is abnormally expressed in cancer tissues (27,31). APAF1 is downregulated in human colorectal cancer, and its expression is associated with adverse patient prognosis (32,33).…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer

Huang

et al. 2017

International Journal of Oncology

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MicroRNAs are a class of small non-coding, endogenous RNAs involved in cancer development and progression. MicroRNA-221 (mir-221) has been reported to have both an oncogenic and tumor-suppressive role in human tumors, but the role of miR-221 in ovarian cancer is poorly understood. In the present study, the expression levels of miR-221 and the apoptosis protease activating factor 1 (APAF1) protein in 63 samples of ovarian cancer tissues and the cell lines, IOSE25, A2780, OVCAR3, SKOV3 and 3AO were detected by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. Cell proliferation was measured using Cell Counting kit-8 (CCK-8); cell migration and invasion were detected using a Transwell assay; cell apoptosis was evaluated by flow cytometry and Hoechst staining, and a luciferase assay was performed to verify a putative target site of miR-221 in the 3′-UTR of APAF1 mRNA. Expression of miR-221 was upregulated in ovarian cancer tissues. Patients with increased miR-221 expression levels had a reduced disease-free survival (P=0.0014) and overall survival (P=0.0058) compared with those with low miR-221 expression. Transfection of SKOV3 and A2780 cell lines with miR-221 inhibitor induced APAF1 protein expression, suppressed cell proliferation and migration and promoted tumor cell apoptosis. In conclusion, the APAF1 gene was confirmed as a direct target of miR-221 and overexpression of APAF1 suppressed ovarian cancer cell proliferation and induced cell apoptosis in vitro. These findings indicate that miR-221-APAF1 should be studied further as a potential new diagnostic or prognostic biomarker for ovarian cancer.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer

Huang

et al. 2017

International Journal of Oncology

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“…Expression of the APAF-1 gene is subjected to a very complex regulation including transcriptional regulation by E2F-1 and p53, epigenetic regulation by histone deacetylases and methylation of the APAF-1 gene and suppression by several miRNAs [51–53]. How Nrf2 might interact with any of these systems known to regulate Apaf-1 levels remains for further investigation.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial permeabilization without caspase activation mediates the increase of basal apoptosis in cells lacking Nrf2

Ariza

González-Reyes

Jódar

et al. 2016

Free Radical Biology and Medicine

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Nuclear factor E2-related factor-2 (Nrf2) is a cap’n’collar/basic leucine zipper (b-ZIP) transcription factor which acts as sensor of oxidative and electrophilic stress. Low levels of Nrf2 predispose cells to chemical carcinogenesis but a dark side of Nrf2 function also exists because its unrestrained activation may allow the survival of potentially dangerous damaged cells. Since Nrf2 inhibition may be of therapeutic interest in cancer, and a decrease of Nrf2 activity may be related with degenerative changes associated with aging, it is important to investigate how the lack of Nrf2 function activates molecular mechanisms mediating cell death. Murine Embryonic Fibroblasts (MEFs) bearing a Nrf2 deletion (Nrf2KO) displayed diminished cellular growth rate and shortened lifespan compared with wild-type MEFs. Basal rates of DNA fragmentation and histone H2A.X phosphorylation were higher in Nrf2KO MEFs, although steady-state levels of reactive oxygen species were not significantly increased. Enhanced rates of apoptotic DNA fragmentation were confirmed in liver and lung tissues from Nrf2KO mice. Apoptosis in Nrf2KO MEFs was associated with a decrease of Bcl-2 but not Bax levels, and with the release of the mitochondrial pro-apoptotic factors cytochrome c and AIF. Procaspase-9 and Apaf-1 were also increased in Nrf2KO MEFs but caspase-3 was not activated. Inhibition of XIAP increased death in Nrf2KO but not in wild-type MEFs. Mitochondrial ultrastructure was also altered in Nrf2KO MEFs. Our results support that Nrf2 deletion produces mitochondrial dysfunction associated with mitochondrial permeabilization, increasing basal apoptosis through a caspase-independent and AIF-dependent pathway.

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“…Many mechanisms are involved in drug resistance of various cancer types (Holohan et al, ). Based on a recent discovery, exosomes released from cancer cells could be involved in chemoresistance of various tumor types (Corcoran et al, ; Yong et al, ). Exosomes derived from cancer cells could regulate processes involved in drug efflux.…”

Section: Exosomes and Cancermentioning

confidence: 99%

Diagnostic and Therapeutic Potential of Exosomes in Cancer: The Beginning of a New Tale?

Mirzaei

Sahebkar

Jaafari

et al. 2017

Journal Cellular Physiology

134

161

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Exosomes have emerged as one of the main players in intercellular communication. These small nano-sized particles have many roles in various physiological pathways in normal and abnormal cells. Exosomes can carry various cargos such as proteins, mRNAs, and miRNAs to recipient cells. Uptake of exosomes and their cargo can induce and/or inhibit different cellular and molecular pathways that lead to the alteration of cell behavior. Multiple lines of evidence have indicated that exosomes released from cancer cells can effect development of cancer in different stages. These particles and their cargo could regulate different processes such as tumor growth, metastasis, drug resistance, angiogenesis, and immune system functioning. It has been observed that exosomes can be used as potential diagnostic biomarkers in various cancer types. Moreover, some studies have used these particles as biological vehicles for delivery of various drugs such as doxorubicin, siRNAs, and miRNAs. Here, we summarized the findings on the role of exosomes in different pathological processes involved in cancer. Moreover, application of these particles as diagnostic and therapeutic biomarkers in different types of cancers is discussed. J. Cell. Physiol. 232: 3251-3260, 2017. © 2016 Wiley Periodicals, Inc.

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The Involvement of miR-23a/APAF1 Regulation Axis in Colorectal Cancer

Cited by 30 publications

References 31 publications

Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer

Overexpression of miRNA-221 promotes cell proliferation by targeting the apoptotic protease activating factor-1 and indicates a poor prognosis in ovarian cancer

Mitochondrial permeabilization without caspase activation mediates the increase of basal apoptosis in cells lacking Nrf2

Diagnostic and Therapeutic Potential of Exosomes in Cancer: The Beginning of a New Tale?

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