Taxane is a family of front-line chemotherapeutic agents against ovarian cancer (OC). The therapeutic efficacy is frequently counteracted by the development of chemoresistance, leading to high rates of relapse in OC patients. The role(s) of microRNAs (miRNAs) in cancer chemoresistance had been supported by many evidences Epigenetic regulation by miRNAs has been reported to influence cancer development and response to therapeutics, however, their role in OC resistance to paclitaxel (PTX) is unclear. Here, we conducted miRNA profiling in the responsive and PTX-resistant OC cell lines before and after treatment with epigenetic modulators. We reveal 157 miRNAs to be downregulated in the PTX-resistant cells compared to parental controls. The expression of five miRNAs (miRNA-7-5p, -204-3p, -501-5p, -3652 and -4286) was restored after epigenetic modulation, which was further confirmed by qPCR. In silico analysis of the signaling pathways targeted by the selected miRNAs identified the PI3K-AKT pathway as the primary target. Subsequent cDNA array analysis confirmed multiple PI3K-AKT pathway members such as AKT2, PIK3R3, CDKN1A, CCND2 and FGF2 to be upregulated in PTX-resistant cells. STRING analysis showed the deregulated genes in PTX-resistant cells to be primarily involved in cell cycle progression and survival. Thus, high throughput miRNA and cDNA profiling coupled with pathway analysis and data mining provide evidence for epigenetically regulated miRNAs-induced modulation of signaling pathways in PTX resistant OC cells. It paves the way to more in-depth mechanistic studies and new therapeutic strategies to combat chemoresistance.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804410 | PMC |
| http://dx.doi.org/10.1038/s41598-020-78596-5 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Inhibition of XIST restrains paclitaxel resistance in breast cancer cells by targeting hsa-let-7d-5p/ATG16L1 through regulation of autophagy.
Cell Signal
December 2024
Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, Anhui, China. Electronic address:
Breast cancer is a fatal malignant tumor in women worldwide. The development of paclitaxel resistance remains a challenge. Autophagy is considered to have a significant part in the chemotherapeutic stress mechanism.
View Article and Find Full Text PDFIvermectin Enhances Paclitaxel Efficacy by Overcoming Resistance Through Modulation of in Non-small Cell Lung Cancer.
Anticancer Res
December 2024
Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan.
Background/aim: Chemoresistance to paclitaxel (PTX) significantly ameliorates therapeutic efficacy in patients with non-small cell lung cancer (NSCLC), especially in advanced stages, deteriorating the progression free and overall survival rates. One of the critical mechanisms contributing to drug resistance is the excretion of PTX from target cells via efflux pumps. Ivermectin was developed as a bactericidal agent against parasites; however, it has recently been shown to inhibit the proliferation of human cancer cells.
View Article and Find Full Text PDFThe superiority of PMFs on reversing drug resistance of colon cancer and the effect on aerobic glycolysis-ROS-autophagy signaling axis.
Oncol Res
November 2024
Department of Pharmacy, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
Background: Polymethoxylated flavones (PMFs) are compounds present in citrus peels and other Rutaceae plants, which exhibit diverse biological activities, including robust antitumor and antioxidant effects. However, the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown. In the present study, we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.
View Article and Find Full Text PDFProtein arginine methyltransferase 5 confers the resistance of triple-negative breast cancer to nanoparticle albumin-bound paclitaxel by enhancing autophagy through the dimethylation of ULK1.
Toxicol Appl Pharmacol
December 2024
Department of Thyroid, Breast and Vascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China. Electronic address:
Chemotherapy remains the major strategy for treating triple-negative breast cancer (TNBC); however, frequently acquired chemoresistance greatly limits the treatment outcomes. Protein arginine methyltransferase 5 (PRMT5), which modulates arginine methylation, is important in chemoresistance acquisition across various cancers. The function of PRMT5 in the development of chemoresistance in TNBC is still not well understood.
View Article and Find Full Text PDFSTUB1 suppresses paclitaxel resistance in ovarian cancer through mediating HOXB3 ubiquitination to inhibit PARK7 expression.
Commun Biol
November 2024
Department of Gynecology and obstetrics, Guizhou Provincial People's Hospital, Guiyang, 550002, China.
Article Synopsis
- Paclitaxel is a key treatment for ovarian cancer, but its effectiveness can be hindered by resistance mechanisms involving proteins like STUB1.
- Researchers used various methods to analyze gene and protein levels, cell growth, and mitochondrial changes, discovering that STUB1 is reduced and PARK7 is increased in chemotherapy-resistant ovarian cancer tissues and cells.
- The study highlights that overexpressing STUB1, or silencing PARK7, can decrease cell growth and encourage ferroptosis in resistant cells, indicating STUB1's role in regulating the HOXB3/PARK7 pathway to combat chemotherapy resistance.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!