MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

Du, Juan; Wang, Lina; Li, Chenxi; Yang, Huilun; Li, Yuanbo; Hu, Haiyang; Li, Hui; Zhang, Zongfeng

doi:10.1007/s13277-015-4247-8

Cited by 47 publications

(31 citation statements)

References 31 publications

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“…Mechanically, at the upstream of Akt, PTEN elicits its phosphatase activity and inhibit the establishment of phosphatidylinositol‐3, 4, 5‐trisphosphate (PIP3) from phosphatidylinositol‐4, 5‐bisphosphate (PIP2), thus antagonizing the activity of PI3 kinase (PI3K) and leading to Akt dephosphorylation . In recent research, PTEN has been accepted as a target of microRNA‐221, and reported to affect the gefitinib‐resistance of cervical cancer cells . As for our research, we report that PTEN is crucial for microRNA‐221‐mediated breast cancer resistance to chemotherapy.…”

Section: Discussionmentioning

confidence: 58%

MicroRNA‐221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling

Yin

Wang

et al. 2020

Cancer Medicine

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As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA‐221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA‐221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF‐7/ADR) compared to its parental line (MCF‐7) and the normal breast epithelial cell line (MCF‐10A). Enforced level of microRNA‐221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA‐221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF‐7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA‐221, which was conversely associated with a microRNA‐221 level in breast tumors. The knock‐down of PTEN partially reversed the stimulatory role of microRNA‐221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA‐221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA‐221/PTEN axis may act as a promising strategy for the treatment of chemotherapy‐resistant breast tumors.

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Section: Discussionmentioning

confidence: 58%

MicroRNA‐221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling

Yin

Wang

et al. 2020

Cancer Medicine

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“…Gefitinib as single or combinative therapeutic agent has also been reported in clinical trials of breast cancer (Segovia-Mendoza et al , 2015), ovarian cancer (Posadas et al , 2007), pancreatic cancer (Brell et al , 2009), and cervical cancer (Goncalves et al , 2008). The mechanisms of action for gefitinib on these cancers include modulation of EGFR pathways such as PI3K/Akt, Raf1/Erk1/2, and cell cycle arrest (Zhou et al , 2009; Ohta et al , 2012; Segovia-Mendoza et al , 2015; Du et al , 2016). Therefore, gefitinib and LMB treatment may also be effective in treating these cancers with similar synergistic mechanisms as reported in our study.…”

Section: Discussionmentioning

confidence: 99%

Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells

Liu

Gao

2017

Toxicology and Applied Pharmacology

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib has demonstrated dramatic clinical efficacy in non-small cell lung cancer (NSCLC) patients. However, its therapeutic efficacy is ultimately limited by the development of acquired drug resistance. The aim of this study was to explore the potential utility of chromosome region maintenance 1 (CRM1) inhibitor leptomycin B (LMB) in combination with gefitinib to overcome primary and acquired gefitinib resistance in NSCLC cells. The combinative effects of gefitinib and LMB were evaluated by MTT and its underlining mechanism was assessed by flow cytometry and Western blot. LMB displayed a synergistic effect on gefitinib- induced cytotoxicity in A549 (IC50: 25.0±2.1 μM of gefitinib+LMB vs. 32.0±2.5 μM of gefitinib alone, p<0.05). Gefitinib+LMB caused a significantly different cell cycle distribution and signaling pathways involving in EGFR/survivin/p21 compared with gefitinib. A549 cells then were treated with progressively increasing concentrations of gefitinib (A549GR) or in combination with LMB (A549GLR) over 10 months to generate gefitinib resistance. IC50 of gefitinib in A549GLR (37.0±2.8 μM) was significantly lower than that in A549GR (53.0±3.0 μM, p<0.05), which indicates that LMB could reverse gefitinib-induced resistance in A549. Further mechanism investigation revealed that the expression patterns of EGFR pathway and epithelial- mesenchymal transition (EMT) markers in A549, A549GR, and A549GLR were significantly different. In conclusion, LMB at a very low concentration combined with gefitinib showed synergistic therapeutic effects and ameliorated the development of gefitinib- induced resistance in lung cancer cells.

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“…For instance, up-regulation of miR-221 can reduce the sensitivity of cervical cancer cells to gefitinib through the PTEN/PI3K/Akt signaling pathway. 37 Likewise, miR-125b and miR-218 suppress cervical tumor growth activity by targeting the PI3K/Akt/mTOR signaling pathway. 38,39 FOXO1 and p27(Kip1), 2 key effectors of PI3K/Akt signaling, are direct targets of miR-196a.…”

Section: Discussionmentioning

confidence: 99%

Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach

Nair¹,

Manasa²,

Sinto³

et al. 2018

Int J Gynecol Cancer

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MicroRNA-221 targets PTEN to reduce the sensitivity of cervical cancer cells to gefitinib through the PI3K/Akt signaling pathway

Cited by 47 publications

References 31 publications

MicroRNA‐221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling

MicroRNA‐221 promotes breast cancer resistance to adriamycin via modulation of PTEN/Akt/mTOR signaling

Leptomycin B reduces primary and acquired resistance of gefitinib in lung cancer cells

Differential Expression of MicroRNAs in Uterine Cervical Cancer and Its Implications in Carcinogenesis; An Integrative Approach

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