MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma

Sun, Yangbai; He, Na; Dong, Yang; Jiang, Cen

doi:10.1038/srep34238

Cited by 31 publications

(22 citation statements)

References 40 publications

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“…At present, chemotherapy is still an effective treatment to kill OS cells and prolong the life of patients. However, repeated use of chemotherapeutic drugs induces inevitable multiple drug resistance in cancer cells (2,3). Reliable strategies are urgently required to reverse the multiple drug resistance of OS.…”

Section: Introductionmentioning

confidence: 99%

Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2

Shang

Guo

et al. 2017

International Journal of Oncology

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Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells. As a potential strategy, we found that co-treatment with metformin significantly decreased the half maximal inhibitory concentration (IC50) of cisplatin to HOS OS stem cells by downregulating the expression of PKM2. PKM2 downregulation resulted in, metformin inhibited glucose uptake, lactate production and ATP production in HOS CSCs. Therefore, metformin impaired the resistance of HOS CSCs to cisplatin and promoted cisplatin-induced apoptosis. In addition, antitumor effects of other chemotherapeutic drugs such as doxorubicin and 5-fluorouracil were proved to be enhanced by metformin on OS stem cells.

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Section: Introductionmentioning

confidence: 99%

Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2

Shang

Guo

et al. 2017

International Journal of Oncology

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“…increasing research in recent years has verified that miRNAs play important regulatory roles in genesis and development of tumor cells. miRNAs have their own expression profiles in different malignant tumor tissues, as is demonstrated (11). Furthermore, it is also revealed that multiple miRNA molecules participate in regulating important biological processes of cancer cells through silencing expression of cancer cell growth-related genes, thus indirectly exerting tumor-promoting and tumorsuppressing functions (8).…”

Section: Discussionmentioning

confidence: 86%

MicroRNA-152 inhibits cell proliferation of osteosarcoma by directly targeting Wnt/β-catenin signaling pathway in a DKK1-dependent manner

Zhao

Sun²,

et al. 2018

Oncol Rep

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The function of microRNA‑152 for a cohort of patients with osteosarcoma and the influence on cell growth of osteosarcoma were studied. The expression of microRNA‑152 was downregulated in patients with osteosarcoma. The downregulation of microRNA‑152 promotes cell proliferation, decreases apoptosis, and suppresses LDH activity, caspase-3/9 activities and Bax/Bcl-2 and p53 protein expression levels of osteosarcoma through activation of the Wnt/β-catenin signaling pathway by targeting DKK1. Whereas, overexpression of microRNA‑152 targets DKK1 to inhibit cell proliferation, induce apoptosis, and promote LDH activity, caspase-3/9 activities and Bax/Bcl-2 and p53 protein expression levels of osteosarcoma through inactivation of the Wnt/β-catenin signaling pathway. The promotion of DKK1 reversed the anticancer function of microRNA‑152 over-expression through Wnt/β-catenin signaling pathway. We demonstrated that microRNA‑152 inhibits cell proliferation of osteosarcoma through DKK1 by directly targeting Wnt/β‑catenin signaling pathway.

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“…However, transfection with TAZ plasmid abolished the effect of miR-26b ( Figure 5B). As the downstream of cytochrome c release, we observed that combination with cisplatin and miR-26b induced significant cleavage of caspase-9 and caspase-3 which are effectors of intrinsic apoptosis 22,23 (Figure 5C). And finally, restoration of miR-26b expression increased the apoptotic rate of PC9/ R and A549/R cells which were under the cisplatin treatment through suppression of TAZ ( Figure 5D).…”

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

confidence: 95%

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

Zang

Zhao

Gao

et al. 2019

OTT

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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.

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MiR-24-BIM-Smac/DIABLO axis controls the sensitivity to doxorubicin treatment in osteosarcoma

Cited by 31 publications

References 40 publications

Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2

Metformin increases sensitivity of osteosarcoma stem cells to cisplatin by inhibiting expression of PKM2

MicroRNA-152 inhibits cell proliferation of osteosarcoma by directly targeting Wnt/β-catenin signaling pathway in a DKK1-dependent manner

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

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