Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer

Sun, Pengming; Song, Yu; Liu, Dabin; Liu, Guifen; Mao, Xiaodan; Dong, Bin; Braicu, Elena Ioana; Sehouli, Jalid

doi:10.1038/s41598-018-31030-3

Cited by 21 publications

(17 citation statements)

References 43 publications

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“…In our work, we proved that serum exosomal miR-744 is downregulated in HCC tissues. In addition, we identified that a direct target of miR-744 is PAX2, which has been indicated to regulate the chemotherapy response in several cancers [32–34]. In HCC, PAX2 is in high expression level in cancer tissues compared with adjacent normal tissues, which is contrary to the expression of miR-744.…”

Section: Discussionmentioning

confidence: 99%

Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2

Wang

Zhao

Wang³

et al. 2019

Med Sci Monit

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BackgroundHepatocellular carcinoma (HCC) is a commonly occurring liver malignancy. Its prognosis remains unsatisfactory. Accumulating evidence has revealed that exosomal microRNAs (miRNAs) act as biomarkers and play crucial roles in the advancement of HCC. The current study explored the biological role and fundamental mechanism of exosomal miR-744 in HCC.Material/MethodsThe serum exosomes of HCC patients were isolated by differential ultracentrifugation. MiR-744 expression in HCC tissues, cell lines and serum exosomes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU (5-ethynyl-2′-deoxyuridine) assay and Cell Counting Kit-8 (CCK-8) assay were conducted to show the impacts of miR-744 or exosomal miR-744 on proliferation and sorafenib resistance in HepG2 cells. The target of miR-744 was ascertained by regulating the level of miR-744 in HepG2 cells.ResultsMiR-744 is downregulated in HCC tissues and cell lines as well as in exosomes derived from patient serum and HepG2 cells. Additionally, downregulated miR-744 promotes HepG2 cell proliferation and inhibits the chemosensitivity of HepG2 cells to sorafenib. PAX2 was identified as the functional target of miR-744. Interestingly, miR-744 is decreased in exosomes derived from sorafenib-resistant HepG2 cells. Furthermore, when treated with the miR-744-enriched exosomes, the proliferation of HepG2 cells was significantly suppressed, and the sorafenib resistance was reduced.ConclusionsMiR-744 has an imperative role in the propagation and chemoresistance of HCC. Serum exosomal miR-744 might act as a biomarker of HCC, and exosomal miR-744 might offer an innovative strategy for HCC treatment.

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Section: Discussionmentioning

confidence: 99%

Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2

Wang

Zhao

Wang³

et al. 2019

Med Sci Monit

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“…Cisplatin has been the chemotherapy of choice against OC for a long time 14 and the development of resistance against cisplatin remains a major clinical hindrance in the effective therapy of OC patients 15 . Role of several factors 16 , 17 , including epigenetic factors 18 has been pursued in the acquired cisplatin resistance in OC. Additionally, in recent years, a number of lncRNAs have been proposed/investigated for their possible role in cisplatin sensitivity and resistance.…”

Section: Introductionmentioning

confidence: 99%

Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling

Tan

Sun

Shangguan

et al. 2020

Sci Rep

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Ovarian Cancer (OC) is a highly lethal gynecological cancer which often progresses through acquired resistance against the administered therapy. Cisplatin is a common therapeutic for the treatment of OC patients and therefore it is critical to understand the mechanisms of resistance against this drug. We studied a paired cell line consisting of parental and cisplatin resistant (CR) derivative ES2 OC cells, and found a number of dysregulated lncRNAs, with CHRF being the most significantly upregulated lncRNA in CR ES2 cells. The findings corroborated in human patient samples and CHRF was significantly elevated in OC patients with resistant disease. CHRF was also found to be elevated in patients with liver metastasis. miR-10b was found to be mechanistically involved in CHRF mediated cisplatin resistance. It induced resistance in not only ES2 but also OVCAR and SKOV3 OC cells. Induction of epithelial-to-mesenchymal-transition (EMT) and activation of STAT3 signaling were determined to be the mechanisms underlying the CHRF-miR-10b axis-mediated cisplatin resistance. Down-regulation of CHRF reversed EMT, STAT3 activation and the resulting cisplatin resistance, which could be attenuated by miR-10b. The results were also validated in an in vivo cisplatin resistance model wherein CR cells were associated with increased tumor burden, CHRF downregulation associated with decreased tumor burden and miR-10b again attenuated the CHRF downregulation effects. Our results support a novel role of lncRNA CHRF in cisplatin resistance of OC and establish CHRF-miR-10b signaling as a putative therapeutic target for sensitizing resistant OC cells.

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“…These are CDKN2A [11,23], RB1 [10,11] ], PIK3CA [12], AKT3, HOXD8 [12], PAX5 [23], MAP3K8 [24], and MITF [12]. All these genes are either involved in the regulation of the aforementioned MAPK and PI3K/AKT signaling pathways or they are tumor suppressors affecting drug resistance in other cancers (HOXD8, [25]; PAX5, [26]). The panel of selected genes and variants is of course not exhaustive and there are other putative genetic biomarkers of melanoma resistance to be discovered.…”

Section: Introductionmentioning

confidence: 99%

Genetic Profiling of Advanced Melanoma: Candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy

et al. 2020

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Background Molecularly targeted therapy has revolutionized the treatment of advanced melanoma. However, despite its high efficiency, a majority of patients experience relapse within 1 year of treatment because of acquired resistance, and approximately 10-25% patients gain no benefit from these agents owing to intrinsic resistance. This is mainly caused by the genetic heterogeneity of melanoma cells. Objective We aimed to validate the predictive significance of selected genes in advanced melanoma patients before treatment with BRAF/MEK inhibitors. Patients and Methods Archival DNA derived from 37 formalin-fixed paraffin-embedded pre-treatment advanced melanoma samples of patients treated with targeted therapy was used for next-generation sequencing analysis using the Ion Torrent platform. The AmpliSeq Custom Panel comprised coding sequences or hot spots of 23 melanoma genes: ATM,

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Potential role of the HOXD8 transcription factor in cisplatin resistance and tumour metastasis in advanced epithelial ovarian cancer

Cited by 21 publications

References 43 publications

Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2

Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2

Novel role of lncRNA CHRF in cisplatin resistance of ovarian cancer is mediated by miR-10b induced EMT and STAT3 signaling

Genetic Profiling of Advanced Melanoma: Candidate Mutations for Predicting Sensitivity and Resistance to Targeted Therapy

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