Reversal of Paclitaxel Resistance in Epithelial Ovarian Carcinoma Cells by a MUC1 Aptamer-let-7i Chimera

Liu, Nenghui; Zhou, Can; Zhao, Jingfeng; Chen, Yuxiang

doi:10.3109/07357907.2012.707265

Cited by 64 publications

(40 citation statements)

References 18 publications

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“…The let-7 isoforms let-7i and miR-98 were shown to decrease expression of PGRMC1 in SKOV-3 ovarian cancer cells in response to P4 treatment [56]. A study by Liu et al fuither supports this idea in which a MUCl aptamer-let7i chime1ic system was used to selectively deliver let7i miRNAs to OVCAR-3 cells [57]. The result was a decrease in PGRMC1 expression and concomitant increase in chemosensitivity to paclitaxel treatment.…”

Section: Discussionmentioning

confidence: 99%

Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

et al. 2015

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Endometrial cancer is the leading gynecologic cancer in women in the United States with 52,630 women predicted to be diagnosed with the disease in 2014. The objective of this study was to determine if progesterone (P4) receptor membrane component 1 (PGRMC1) influenced endometrial cancer cell viability in response to chemotherapy in vitro and in vivo. A Jentiviral-based shRNA knockdown approach was used to generate stable PGRMC1-intact and PGRMC1-deplete Ishikawa endometrial cancer cell lines that also lacked expression of the classical progesterone receptor (PGR). Progesterone treatment inhibited mitosis of PGRMC1-intact, but not PGRMC1-deplete cells, suggesting that PGRMC1 mediates the anti-mitotic actions of P4.To test the hypothesis that PGRMC1 attenuates chemotherapy-induced apoptosis, PGRMC1-intact and PGRMC1-deplete cells were treated in vitro with vehicle, P4 (1 μM), doxorubicin (Dox. 2 μg/ml). or P4 + Dox for 48 h. Doxorubicin treatment of PGRMC1-intact cells resulted in a significant increase in cell death; however, co-treatment with P4 significantly attenuated Dex-induced cell death. This response to P4 was lost in PGRMC1-deplete cells. To extend these observations in vivo, a xenograft model was employed where PGRMC1-intact and PGRMC1-deplete endometrial tumors were generated following subcutaneous and intraperitonea l inoculation of immunocompromised NOD/SCIO and nude mice, respectively. Tumors derived from PGRMC1-deplete cells grew slower than tumors from PGRMC1-intact cells. Mice harboring endometrial tumors were then given three treatments of vehicle (1:1 cremophor EL: ethanol + 0.9% saline) or chemotherapy [Paclitaxel (15 mg/kg, i.p.) followed after an interval of 30 minutes by CARBOplatin (SO mg/kg)] at five day intervals. In response to chemotherapy, tumor volume decreased approximately four-fold more in PGRMC1-deplete tumors when compared with PGRMC1 intact control tumors, suggesting that PGRMC1 promotes tumor cell viability during chemotherapeutic stress. In sum, these in vitro and in vivo findings demonstrate that PGRMC1 plays a prominent role in the growth and chemoresistance of human endometrial tumors.

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Section: Discussionmentioning

confidence: 99%

Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

et al. 2015

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“…Among them, miRNA let-7i was the first member of the miRNA family identified to be associated with tumor drug sensitivity, and was observed to play an indirect anti-tumor role by increasing the cell sensitivity to chemotherapeutic drugs (13). Lee et al (14) demonstrated that the expression of let-7i was decreased in platinum-resistant ovarian tumor cells, and downregulation of the expression of let-7i could increase ovarian cancer resistance to cisplatin, suggesting that let-7i could be used as a chemical marker to evaluate the prognosis of ovarian cancer.…”

Section: Introductionmentioning

confidence: 99%

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

Liu

et al. 2016

Oncology Letters

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Abstract. The present study aimed to explore the expression of microRNA (miRNA or miR) in drug-resistant and drug-sensitive ovarian cancer cell lines, and to seek the potential therapeutic target of ovarian cancer drug-resistant mechanism in order to improve drug resistance by altering miRNA levels. The drug-resistant characteristics of SKOV3/DDP, SKOV3, COC1/DDP and COC1 cell lines were studied. The miRNAs that were differentially expressed between cisplatin-resistant cells and its parental cells in ovarian cancer were screened with a miRNA chip. The effect of miRNAs was detected, and their drug-resistant mechanism was investigated by transfection and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide methods. Among the expression screening of miRNAs, 41 mRNAs, including Homo sapiens (hsa)-miR-30a-5p and hsa-miR-34c-5p, were highly expressed in the drug-resistant cells, whereas 44 miRNAs, including hsa-miR-96-5p and hsa-miR-200c-3p, were lowly expressed. The expression levels of hsa-miR-30a-5p in two types of ovarian cancer chemotherapy-resistant cell lines were significantly higher than those in chemotherapy-sensitive cell lines, which was associated with ovarian cancer chemotherapy resistance. In conclusion, high expression of miRNA-30a-5p was able to promote cell growth and colony forming ability, and enhance cell migration and invasion. Thus, miRNA-30a-5p is expected to become a meaningful novel target for ovarian cancer resistant treatment.

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“…Let-7a, another tumor suppressor miRNA that belongs to let-7 family, has also been proposed as a potential biomarker for determining response to paclitaxel [251]. With the objective of delivering let-7i specifically to OC cells, let-7i was combined with MUC1 aptamer [252]. Once delivered, let-7i was observed to down-regulate cell cycle-associated factors, resulting in reversal of paclitaxel resistance.…”

Section: Biological Significance Of Mirnas In Gynecologic Cancersmentioning

confidence: 99%

MicroRNAs in gynecological cancers: Small molecules with big implications

et al. 2017

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Gynecological cancers (GCs) are often diagnosed at advanced stages, limiting the efficacy of available therapeutic options. Thus, there remains an urgent and unmet need for innovative research for the efficient clinical management of GC patients. Research over past several years has revealed the enormous promise of miRNAs. These small non-coding RNAs can aid in the diagnosis, prognosis and therapy of all major GCs, viz., ovarian cancers, cervical cancers and endometrial cancers. Mechanistic details of the miRNAs-mediated regulation of multiple biological functions are under constant investigation, and a number of miRNAs are now believed to influence growth, proliferation, invasion, metastasis, chemoresistance and the relapse of different GCs. Modulation of tumor microenvironment by miRNAs can possibly explain some of their reported biological effects. miRNA signatures have been proposed as biomarkers for the early detection of GCs, even the various subtypes of individual GCs. miRNA signatures are also being pursued as predictors of response to therapies. This review catalogs the knowledge gained from collective studies, so as to assess the progress made so far. It is time to ponder over the knowledge gained, so that more meaningful pre-clinical and translational studies can be designed to better realize the potential that miRNAs have to offer.

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Reversal of Paclitaxel Resistance in Epithelial Ovarian Carcinoma Cells by a MUC1 Aptamer-let-7i Chimera

Cited by 64 publications

References 18 publications

Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

Progesterone receptor membrane component 1 deficiency attenuates growth while promoting chemosensitivity of human endometrial xenograft tumors

Expression of microRNA-30a-5p in drug-resistant and drug-sensitive ovarian cancer cell lines

MicroRNAs in gynecological cancers: Small molecules with big implications

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