miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression

Li, Jian; Chen, Yuxiang; Zhao, Jingfeng; Kong, Fangren; Yang-de, Zhang

doi:10.1016/j.canlet.2011.02.003

Cited by 107 publications

(101 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The uncertainty of miR-203 function may be due to its targeted activity against numerous molecules involved in a variety of cellular functions. Some of its targets include p63, Akt2, BMI1, and LASP1 which are responsible for cellular proliferation, apoptosis, and chemoresistance (40)(41)(42)(43)(44)(45)(46). Even though our results are consistent with previously published data, we acknowledged that our study has some limitations.…”

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Isupporting

confidence: 84%

“…Considering these data, our results support the hypothesis that miR-203 acts as a tumor suppressor gene by regulating Puma expression in both colon and lung cancer cells. However, Li et al (40) reported that p53 negatively regulates the miR-203 function when they found that overexpressed miR-203 decreases chemoresistance in p53-mutated colon cancer cells, but has no effect on p53 wild-type cells. In contrast, Li et al supported our findings by showing that overexpressed miR-203 decreases levels of blc-xL (an anti-apoptotic gene), but increases levels of Bax (a pro-apoptotic gene) (40).…”

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Imentioning

confidence: 99%

“…However, Li et al (40) reported that p53 negatively regulates the miR-203 function when they found that overexpressed miR-203 decreases chemoresistance in p53-mutated colon cancer cells, but has no effect on p53 wild-type cells. In contrast, Li et al supported our findings by showing that overexpressed miR-203 decreases levels of blc-xL (an anti-apoptotic gene), but increases levels of Bax (a pro-apoptotic gene) (40). Clinical data have shown that patients with wild-type p53 colorectal cancer undergoing chemotherapy have significantly better survival than those with mutated p53 (41).…”

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Imentioning

confidence: 99%

See 2 more Smart Citations

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

Funamizu

Lacy

Kamada

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. The present study investigated the relationship between and the p53 upregulated modulator of apoptosis (Puma) in colon (HCT116) and lung cancer (A549) cells. Colon and lung cancer cell lines were selected for this study since a relationship between p53/miR-203 and p53/Puma has been established in both cancers. In the present study, adriamycin and nutlin-3 were used to activate p53, which induced both miR-203 and Puma expression in HCT116 cells. In contrast, HCT 116 cells with downregulated p53 showed decreased miR-203 and Puma expression. Importantly, we found that overexpressed miR-203 in HCT116 cells resulted in significantly increased Puma expression (P<0.05). Based on these findings, we hypothesized that another limb of the p53/Puma axis depends on miR-203 expression. To further validate this relationship, we used lung cancer cells (A549) and found that activated p53 increased both miR-203 and Puma expression. In addition, we found that Puma expression remained elevated in cells with overexpressed miR-203 in the presence of p53 downregulation. Cumulatively, our data purport that p53 not only increased Puma expression directly, but that it may also do so through miR-203. Additionally, functional studies revealed that miR-203 overexpression induced apoptosis and inhibited cell invasiveness.

show abstract

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Isupporting

confidence: 84%

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Imentioning

confidence: 99%

Section: Overexpressed Mir-203 Induces Apoptosis and Decreases Cell Imentioning

confidence: 99%

See 1 more Smart Citation

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

Funamizu

Lacy

Kamada

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Therefore, there may be other molecules or signaling pathways that are also targeted by miR-203 (19,22,(47)(48)(49)(50), and some of them may be still unknown in NPC. This presumption may raise interesting future work to reveal the entire functions of miR-203 in NPC radioresistance.…”

Section: Discussionmentioning

confidence: 99%

“…MiR-203 is frequently downregulated and functions as a potential tumor suppressor in the various types of cancers, including NPC (19)(20)(21). Recent studies showed that the miR-203 expression level positively correlates with chemosensitivity in colon (22) and prostate (23) cancer cells. However, the function and mechanism of miR-203 in tumor radioresistance have not been characterized.…”

Section: Introductionmentioning

confidence: 99%

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA (miR) regulates this phenomenon. In this study, we investigated the function and mechanism of miR-203 in NPC radioresistance, one of downregulated miRs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-203 was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its decrement significantly correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that miR-203 mimic markedly decreased NPC cell radioresistance. In a mouse model, therapeutic administration of miR-203 agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we confirmed that IL8 was a direct target of miR-203, and found that reduced miR-203 promoted NPC cell radioresistance by activating IL8/ AKT signaling. Moreover, the levels of IL8 and phospho-AKT were significantly increased in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and negatively associated with miR-203 level. Our data demonstrate that miR-203 is a critical determinant of NPC radioresponse, and its decrement enhances NPC radioresistance through targeting IL8/AKT signaling, highlighting the therapeutic potential of the miR-203/IL8/AKT signaling axis in NPC radiosensitization. Mol Cancer Ther; 14(11); 2653-64. Ó2015 AACR.

show abstract

MicroRNA Signatures as Biomarkers of Colorectal Cancer

Pfütze

Luo

Burwinkel

2013

MicroRNAs in Medicine

View full text Add to dashboard Cite

miR-203 reverses chemoresistance in p53-mutated colon cancer cells through downregulation of Akt2 expression

Cited by 107 publications

References 37 publications

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

MicroRNA-203 induces apoptosis by upregulating Puma expression in colon and lung cancer cells

MiRNA-203 Reduces Nasopharyngeal Carcinoma Radioresistance by Targeting IL8/AKT Signaling

MicroRNA Signatures as Biomarkers of Colorectal Cancer

Contact Info

Product

Resources

About