Silencing of miR-21 sensitizes CML CD34+ stem/progenitor cells to imatinib-induced apoptosis by blocking PI3K/AKT pathway

Wang, Weizhang; Pu, Qiao-Hong; Li, Xianghua; Liu, Man-Yu; Wu, Lirong; Wu, Qingqing; Chen, Yongheng; Fenfang, Liao; Zhu, Jianhua; Jin, Xiaobao

doi:10.1016/j.leukres.2015.07.008

Cited by 38 publications

(29 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various factors have been reported to contribute to the chronic myeloid leukemia. PI3K-AKT pathway has been identified as a core component of chronic myeloid leukemia associated pathways as we have predicted [65]. Based on recent publications, such pathway (PI3K-AKT pathway) has also been confirmed to be quite crucial for pancreatic cancer, validating our prediction [66].…”

Section: Resultssupporting

confidence: 79%

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

Yin

Wang

Zhang

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Pancreatic cancer is a serious disease that results in more than thirty thousand deaths around the world per year. To design effective treatments, many investigators have devoted themselves to the study of biological processes and mechanisms underlying this disease. However, it is far from complete. In this study, we tried to extract important gene ontology (GO) terms and KEGG pathways for pancreatic cancer by adopting some existing computational methods. Genes that have been validated to be related to pancreatic cancer and have not been validated were represented by features derived from GO terms and KEGG pathways using the enrichment theory. A popular feature selection method, minimum redundancy maximum relevance, was employed to analyze these features and extract important GO terms and KEGG pathways. An extensive analysis of the obtained GO terms and KEGG pathways was provided to confirm the correlations between them and pancreatic cancer.

show abstract

Section: Resultssupporting

confidence: 79%

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

Yin

Wang

Zhang

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Additionally, ectopic expression of miR-217 was found to sensitize dasatinib-resistant K562 cells to dasatinib (20). More recently, downregulation of miR-21 increased apoptosis in CML (21). However, the role of miRNAs in the drug resistance of leukemia has not been fully addressed.…”

Section: Discussionmentioning

confidence: 99%

miR-9 regulates the multidrug resistance of chronic myelogenous leukemia by targeting ABCB1

Zhao

et al. 2017

Oncology Reports

View full text Add to dashboard Cite

Multidrug resistance (MDR) is commonly correlated with the poor prognosis of chronic myelogenous leukemia. Aberrant expression of microRNAs (miRNAs) plays an important role in the MDR of various types of cancers. MicroRNA-9 (miR-9) has been confirmed to be dysregulated in many types of cancers. However, the relationship between miR-9 and MDR in chronic myelogenous leukemia (CML) remains largely unknown. In the present study, we showed that miR‑9-3p (miR-9) was downregulated in adriamycin (ADR)‑resistant K562/ADR cells and CML/MDR patients. Overexpression of miR-9 was sufficient to reverse cancer cell resistance to multiple chemotherapeutics in vitro and sensitized tumors to chemotherapy in vivo. Furthermore, we found that ABCB1 is a direct target of miR-9. These findings suggest that miR-9 plays a critical role in MDR in CML by targeting ABCB1. These results provide new evidence of miR-9 as a biomarker for clinical diagnosis and as a potential therapeutic target for CML.

show abstract

“…Interestingly, blocking miR-21 in SCC13 reduced the number of ALDH+ cells. This was predicted as miR-21 inhibition was shown to reduce CSC numbers and to enhance chemosensitivity in tongue SCC [44], lung adenocarcinoma [45], glioblastoma [46], leukemia [47] and other cancers [48]. Combination of both inhibitors was then hypothesized to provide a cumulative benefit similar to the effective combination of PI3K/mTOR inhibitors in reducing T-cell leukemia growth [49].…”

Section: Discussionmentioning

confidence: 99%

Stage-dependent therapeutic efficacy in PI3K/mTOR-driven squamous cell carcinoma of the skin

et al. 2017

View full text Add to dashboard Cite

Cutaneous squamous cell carcinoma (SCC) is a recurrent cancer that is prevalent in predisposed subjects such as immunosuppressed patients and patients being treated for other malignancies. Model systems to trial therapies at different stages of SCC development are lacking, therefore precluding efficient therapeutic interventions. Here, we have disrupted the expression of the tumor suppressor GRHL3 to induce loss of PTEN and activation of the PI3K/mTOR signaling pathway in mice and human skin, promoting aggressive SCC development. We then examined the potential for targeting PI3K/mTOR and an oncogenic driver miR-21, alone and in combination, for the prevention and treatment of SCC during the initiation, promotion/progression and establishment stages. Treatment with PI3K/mTOR inhibitors completely prevented tumor initiation, and these inhibitors significantly delayed the course of papilloma progression to malignancy. However, established SCC did not undergo any growth regression, indicating that this therapy is ineffective in established cancers. Mechanistically, the resistant SCCs displayed increased miR-21 expression in mice and humans where antagonists of miR-21 rescued expression levels of GRHL3/PTEN, but the combination of miR-21 antagonism with PI3K/mTOR inhibition resulted in acquired SCC resistance in part via c-MYC and OCT-4 upregulation. In conclusion, our data provide molecular evidence for the efficacy of targeting oncogenic drivers of SCC during the initiation and promotion stages and indicate that combination therapy may induce an aggressive phenotype when applied in the establishment stage.

show abstract

Silencing of miR-21 sensitizes CML CD34+ stem/progenitor cells to imatinib-induced apoptosis by blocking PI3K/AKT pathway

Cited by 38 publications

References 48 publications

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

Analysis of Important Gene Ontology Terms and Biological Pathways Related to Pancreatic Cancer

miR-9 regulates the multidrug resistance of chronic myelogenous leukemia by targeting ABCB1

Stage-dependent therapeutic efficacy in PI3K/mTOR-driven squamous cell carcinoma of the skin

Contact Info

Product

Resources

About