Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex

Zhang, Rui; Xu, Jian; Zhao, Jian; Bai, Jinghui

doi:10.18632/oncotarget.16779

Cited by 38 publications

(33 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, transfection with TAZ plasmid reduced the collapse of mitochondria in cisplatin and miR-26b co-treated PC9/R and A549/R cells ( Figure 5A). As the results of mitochondria collapse, we next found that overexpression of miR-26b obviously increased the release of cytochrome c which is a mitochondria-derived and key apoptotic inducer 21 into cytosol of PC9/R and A549/R cells. However, transfection with TAZ plasmid abolished the effect of miR-26b ( Figure 5B).…”

Section: Restoration Of Mir-26b Expression Targets Taz To Increase Thmentioning

confidence: 81%

<p>Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin</p>

Zang

Zhao

Gao

et al. 2019

OTT

View full text Add to dashboard Cite

Background: Dysregulation of microRNAs has been reported to be responsible for drug resistance of cancers. However, the association between aberrant expression of miR-26b and cisplatin resistance in non-small cell lung cancer (NSCLC) remains unclear. Methods: PC9 and A549 were used to establish the cisplatin resistance models on NSCLC. Expression of miR-26b in cisplatin-resistant PC9 and A549 cells (PC9/R and A549/R) was detected by quantitative real-time PCR assays. Drug sensitivity and mitochondrial apoptosis were detected by Cell Counting Kit-8 assay and flow cytometry assay, respectively. The target relationship between miR-26b and tafazzin (TAZ) was validated by dual-luciferase reporter assay. Results: Obvious downregulation of miR-26b was observed in PC9/R and A549/R cells. Restoration of miR-26b partially reversed the cisplatin resistance of PC9/R and A549/R cells. Expression of TAZ was increased in PC9/R and A549/R cells compared to the parental PC9 and A549 cells. Results of dual-luciferase reporter assays verified that TAZ was targeted by miR-26b. We showed that restoration of miR-26b expression inhibited the TAZ expression and thus expanded the mitochondrial pathway of apoptosis induced by cisplatin in PC9/ R and A549/R cells. Conclusion: Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting TAZ. miR-26b/TAZ axis may represent a potential strategy to reverse the cisplatin in NSCLC.

show abstract

Section: Restoration Of Mir-26b Expression Targets Taz To Increase Thmentioning

confidence: 81%

<p>Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin</p>

Zang

Zhao

Gao

et al. 2019

OTT

View full text Add to dashboard Cite

show abstract

“…Apaf‐1 is a crucial pro‐apoptotic protein in the mitochondrial apoptosis pathway, with three special structures, of which the caspase recruitment domain (CARD) is the most active. In vertebrates, one of the major mechanisms of caspase activation is to release cytochrome c from mitochondria and then to interact with cell death protein 4 homologue Apaf‐1 (Zhang, Xu, Zhao, & Bai, ). With the assistance of dATP/ATP, caspase binds to cytochrome c, triggers Apaf‐1 oligomerisation, activates procaspase‐3, and further activates caspase‐3 and caspase‐7 (Zhang, Shi et al, ).…”

Section: Discussionmentioning

confidence: 99%

Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

Kong

et al. 2019

Andrologia

View full text Add to dashboard Cite

We aimed to evaluate the effects of dihydroartemisinin (DHA) on heat‐shock protein 70 (HSP70) expression in human prostate cancer PC‐3 cells and to examine the molecular mechanism. The viability of PC‐3 cells following treatment with 25, 50, 100 and 200 μmol/L DHA for 48 hr was detected by flow cytometry and MTT assay. The expression of HSP70 mRNA was detected by RT‐qPCR. The expression levels and locations of HSP70, caspase‐3 and apoptosis‐inducing factor (AIF) were detected with immunofluorescence assay. With 100 μmol/L HSP70 inhibitor quercetin as positive control and dimethyl sulphoxide (DMSO) as solvent control, the protein expressions of HSP70, apoptotic protease activating factor‐1 (Apaf‐1) and AIF were detected by Western blot. DHA promoted PC‐3 cell apoptosis dose‐dependently. With increasing DHA dose, the expression of HSP70 mRNA significantly decreased (p < 0.05). DHA did not change the location of HSP70 or AIF. Compared with control and DMSO groups, the expression of HSP70 protein significantly decreased, and those of Apaf‐1, caspase‐3 and AIF significantly increased following treatment with DHA and quercetin for 48 hr. In conclusion, DHA inhibits the expression of HSP70 and induces the apoptosis of PC‐3 cells. The results provide valuable experimental evidence for prostate cancer therapies using DHA.

show abstract

“…Here, we have elaborated the role of miRNAs in regulating the CSC features in the pathogenesis of various human malignancies (Table 1). MiRNA-215 DTL [59] miR-148a WNT, β-catenin [60] miR-199a/b Gsk3β, Wnt/β-catenin-ABCG2 [61] miR-196b-5p STAT3 [62] miRs-31 EphB2 and EphA2 [63] miR-27a Apaf-1/caspase-9 [64] miR-372/373 Nanog, Hedgehog, NFκB, MAPK/Erk, VDR Jak-STAT, TGF-beta, PI3K-Akt, MAPK. [65,66] miR-137 DCLK1 [67] miR-146a β-catenin [68] miR-195-5p STAT3, BIRC5, BCL2, BCL-XL, SOX2, CD133, RBPJ, Notch2 [62,69] Lung miR-128 AKT/ERK, p38, c-met/PI3K/AKT, VEGF/PI3K/AKT, IL-6-JAK-STAT3 [70][71][72][73] miR-181b Notch2 [74] miR-138 TGFβ [75] miR-5100 Rab6 [76] miR-214 c-MYC [76] miR-708-5p Wnt/β-catenin [77] miR-873 miR-125a-3p…”

Section: Role Of Mirna and Oncogenic Signaling Pathways In Human Cancmentioning

confidence: 99%

“…The oncogenic role of dysregulated miR-27a has been well elucidated in a number of human malignancies including CRC via enhanced cell proliferation, invasion and migration, and EMT. In one of the recent studies, it has been found that overexpression of miR-27a in CRC stem cells which is associated with resistance as knocking down of miR-27a sensitizes CRC stem cells towards apoptosis via activation of the Apaf-1/caspase-9 apoptosome-mediated apoptotic pathway [64].…”

Section: Colorectal Cancermentioning

confidence: 99%

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Khan

Ahmed

Elareer

et al. 2019

Cells

239

168

View full text Add to dashboard Cite

Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment.

show abstract

Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex

Cited by 38 publications

References 38 publications

<p>Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin</p>

<p>Restoration of miR-26b expression partially reverses the cisplatin resistance of NSCLC by targeting tafazzin</p>

Effects of dihydroartemisinin on HSP70 expression in human prostate cancer PC‐3 cells

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Contact Info

Product

Resources

About