scholarly journals MicroRNA-7-5p Promotes Cisplatin Resistance of Cervical Cancer Cells and Modulation of Cellular Energy Homeostasis by Regulating the Expression of the PARP-1 and BCL2 Genes

2018 ◽  
Vol 24 ◽  
pp. 6506-6516 ◽  
Author(s):  
Fengxia Yang ◽  
Li Guo ◽  
Yujing Cao ◽  
Shizhen Li ◽  
Jianhua Li ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Energy Homeostasis ◽  
Cisplatin Resistance ◽  
Cellular Energy ◽  
Cervical Cancer Cells ◽  
Parp 1

scholarly journals Enhancer of mRNA Decapping protein 4 (EDC4) interacts with replication protein a (RPA) and contributes to Cisplatin resistance in cervical Cancer by alleviating DNA damage

Hereditas ◽  
2020 ◽  
Vol 157 (1) ◽  
Author(s):  
Xiaoling Wu ◽  
Youwen Zhong ◽  
Qing Chen ◽  
Xin Zhang ◽  
Hua Zhang
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Mrna Decapping ◽  
Cervical Cancer Cells

Abstract Background Cervical cancer (CC) is the third most common gynecological malignancy around the world. Cisplatin is an effective drug, but cisplatin resistance is a vital factor limiting the clinical usage of cisplatin. Enhancer of mRNA decapping protein 4 (EDC4) is a known regulator of mRNA decapping, which was related with genome stability and sensitivity of drugs. This research was to investigate the mechanism of EDC4 on cisplatin resistance in CC. Two human cervical cancer cell lines, HeLa and SiHa, were used to investigate the role of EDC4 on cisplatin resistance in vitro. The knockdown or overexpression of EDC4 or replication protein A (RPA) in HeLa or SiHa cells was performed by transfection. Cell viability was analyzed by MTT assay. The growth of cancer cells was evaluated by colony formation assay. DNA damage was measured by γH2AX (a sensitive DNA damage response marker) immunofluorescent staining. The binding of EDC4 and RPA was analyzed by immunoprecipitation. Results EDC4 knockdown in cervical cancer cells (HeLa and SiHa) enhanced cisplatin sensitivity and cisplatin induced cell growth inhibition and DNA damage. EDC4 overexpression reduced DNA damage caused by cisplatin and enhanced cell growth of cervical cancer cells. EDC4 could interact with RPA and promote RPA phosphorylation. RPA knockdown reversed the inhibitory effect of EDC4 on cisplatin-induced DNA damage. Conclusion The present results indicated that EDC4 is responsible for the cisplatin resistance partly through interacting with RPA in cervical cancer by alleviating DNA damage. This study indicated that EDC4 or RPA may be novel targets to combat chemotherapy resistance in cervical cancer. Graphical abstract

MiR-181a Promotes Apoptosis and Reduces Cisplatin Resistance by Inhibiting Osteopontin in Cervical Cancer Cells

2019 ◽  
Vol 34 (9) ◽  
pp. 559-565 ◽  
Author(s):  
Xiaofei Xu ◽  
Xiaofei Jiang ◽  
Liping Chen ◽  
Yu Zhao ◽  
Zhihua Huang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Cervical Cancer Cells

scholarly journals MicroRNA-125a-5p targets LIM kinase 1 to inhibit cisplatin resistance of cervical cancer cells

2021 ◽  
Vol 21 (5) ◽  
Author(s):  
Yongqian Xu ◽  
Yujie Zheng ◽  
Yan Duan ◽  
Lin Ma ◽  
Ping Nan
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Lim Kinase ◽  
Lim Kinase 1 ◽  
Cervical Cancer Cells

scholarly journals Insights of Cisplatin Resistance in Cervical Cancer: A Decision Making for Cellular Survival

2021 ◽  
Author(s):  
Elizabeth Mahapatra ◽  
Salini Das ◽  
Souvick Biswas ◽  
Archismaan Ghosh ◽  
Debomita Sengupta ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Platinum Resistance ◽  
Cellular Survival ◽  
Repair Enzymes ◽  
Damage Repair ◽  
Cervical Cancer Cells ◽  
The Impact

The clinical scenario of acquired cisplatin resistance is considered as a major impediment in cervical cancer treatment. Bulky drug-DNA adducts formed by cisplatin elicits DNA damage response (DDR) which either subsequently induces apoptosis in the cervical cancer cells or enables them to adapt with drug assault by invigorating pro-survival molecular cascades. When HPV infected cervical cancer cells encounter cisplatin, a complex molecular interaction between deregulated tumor suppressors, DNA damage-repair enzymes, and prosurvival molecules get initiated. Ambiguous molecular triggers allow cancer cells to cull apoptosis by opting for a survival fate. Overriding of the apoptotic cues by the pro-survival cues renders a cisplatin resistant phenotype in the tumor microenvironment. The present review undrapes the impact of deregulated signaling nexus formed due to crosstalk of the key molecules related to cell survival and apoptosis in orchestrating platinum resistance in cervical cancer.

scholarly journals LncRNA OTUD6B-AS1 Induces Cisplatin Resistance in Cervical Cancer Cells Through Up-Regulating Cyclin D2 via miR-206

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Hou ◽  
Rong Yu ◽  
Haiping Zhao ◽  
Hao Yang ◽  
Yuchong Hu ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Luciferase Reporter ◽  
Cyclin D2 ◽  
Aberrant Expression ◽  
Qrt Pcr ◽  
Cervical Cancer Cells ◽  
Reporter Assays ◽  
Underlying Mechanisms

Cervical cancer is one of the most common gynecological cancers. Cisplatin resistance remains a major hurdle in the successful treatment of cervical cancer. Aberrant expression of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are implicated in cisplatin resistance. However, the regulatory functions of lncRNAs and miRNAs in cervical cancer cisplatin resistance and the underlying mechanisms are still elusive. Our qRT-PCR assays verified that miR-206 levels were down-regulated in cisplatin-resistant cervical cancer cells. The introduction of miR-206 sensitized cisplatin-resistant cervical cancer cells to cisplatin. Our qRT-PCR and luciferase reporter assays showed that Cyclin D2 (CCND2) was the direct target for miR-206 in cervical cancer cells. The cisplatin-resistant cervical cancer cells expressed higher CCND2 expression than the parental cells, whereas inhibition of CCND2 could sensitize the resistant cells to cisplatin treatment. Furthermore, we demonstrated that lncRNA OTUD6B-AS1 was up-regulated in cisplatin-resistant cervical cancer cells, and knocking down OTUD6B-AS1 expression induced re-acquirement of chemosensitivity to cisplatin in cervical cancer cells. We also showed that OTUD6B-AS1 up-regulated the expression of CCND2 by sponging miR-206. Low miR-206 and high OTUD6B-AS1 expression were associated with significantly poorer overall survival. Taken together, these results suggest that OTUD6B-AS1-mediated down-regulation of miR-206 increases CCND2 expression, leading to cisplatin resistance. Modulation of these molecules may be a therapeutic approach for cisplatin-resistant cervical cancer.

Abstract 3149: Identification of genes associated with the cisplatin resistance in cervical cancer cells expressing E545K mutation

2017 ◽  
Author(s):  
Wani Arjumand ◽  
Nicholas Jette ◽  
Jb McIntyre ◽  
Prafull Ghatage ◽  
Corinne M. Doll ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Cervical Cancer Cells

scholarly journals Pentoxifylline Sensitizes Cisplatin-Resistant Human Cervical Cancer Cells to Cisplatin Treatment: Involvement of Mitochondrial and NF-Kappa B Pathways

2020 ◽  
Vol 10 ◽  
Author(s):  
Alejandro Bravo-Cuellar ◽  
Pablo Cesar Ortiz-Lazareno ◽  
Erick Sierra-Díaz ◽  
Fabiola Solorzano-Ibarra ◽  
Anibal Samael Méndez-Clemente ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Public Health Problem ◽  
Major Public Health Problem ◽  
Nf Kappa B ◽  
Apoptotic Protein ◽  
Cervical Cancer Cells ◽  
Parp 1

BackgroundCervical cancer continues to be a major public health problem worldwide, and Cisplatin is used as first-line chemotherapy for this cancer; however, malignant cells exposed to CISplatin (CIS) become insensitive to the effects of this drug. PenToXifylline (PTX) is a xanthine that sensitizes several types of tumor cells to apoptosis induced by antitumor drugs, such as Adriamycin, Carboplatin, and CIS. The effects of PTX on tumor cells have been related to the disruption of the NF-κB pathway, thus preventing the activation of cell survival mechanisms such as the expression of anti-apoptotic genes, the secretion of proinflammatory interleukins, and growth factors.ObjectiveIn this work, we studied the antitumor proprieties of PTX in human SiHa cervical carcinoma cells resistant to CIS.Materials and MethodsSiHa and HeLa cervical cancer cells and their CIS-resistant derived cell lines (SiHaCIS-R and HeLaCIS-R, respectively) were used as in-vitro models. We studied the effects of PTX alone or in combination with CIS on cell viability, apoptosis, caspase-3, caspase-8, and caspase-9 activity, cleaved PARP-1, anti-apoptotic protein (Bcl-2 and Bcl-xL) levels, p65 phosphorylation, cadmium chloride (CdCl2) sensitivity, Platinum (Pt) accumulation, and glutathione (GSH) levels, as well as on the gene expression of GSH and drug transporters (influx and efflux).ResultsPTX sensitized SiHaCIS-R cells to the effects of CIS by inducing apoptosis, caspase activation, and PARP-1 cleavage. PTX treatment also decreased p65 phosphorylation, increased Pt levels, depleted GSH, and downregulated the expression of the ATP7A, ATP7B, GSR, and MGST1 genes.ConclusionPTX reverses the acquired phenotype of CIS resistance close to the sensitivity of parental SiHa cells.

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