Quantitative proteomic analysis identifies novel regulators of methotrexate resistance in choriocarcinoma

Fu, Jun; Zheng, Peng; Zhang, Yi; Shi, Dazun

doi:10.1016/j.ygyno.2020.01.013

Cited by 36 publications

(44 citation statements)

References 36 publications

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“…After four series of EMA-EP protocol increase in β-HCG level of our patient was seen. This can be explained by the fact that 10-20% of cases may develop incomplete response to methotrexate based protocols (14). National Comprehensive Cancer Network (NCCN) guideline for Gestational trophoblastic neoplasia and European Society for Medical Oncology (ESMO) guideline for Gestational trophoblastic disease advise usage of drug combinations with etoposide and platinum agents (12,13).…”

Section: Discussionmentioning

confidence: 99%

“…National Comprehensive Cancer Network (NCCN) guideline for Gestational trophoblastic neoplasia and European Society for Medical Oncology (ESMO) guideline for Gestational trophoblastic disease advise usage of drug combinations with etoposide and platinum agents (12,13). These protocols containing etoposide and platinum agent are effective in methotrexate resistant disease in about 80% of cases (14). We decided to use Charing Cross Hospital EP protocol (etoposide and cisplatin) that is used in organ-failure or life-threatening disease (15).…”

Section: Discussionmentioning

confidence: 99%

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Adjuvant chemotherapy of resistant high risk choriocarcinoma

et al. 2021

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Choriocarcinoma is a subtype of gestational trophoblastic disease. It is a very rare neoplasm, with incidence of about 1 case in 40.000 pregnancies. Gestational form of choriocarcinoma arises most commonly after abortion, while nongestational form develops from pluripotent germ cells. Choricarcinoma is highly malignant and highly chemosensitive type of tumor. A 43-year-old patient diagnosed with extra uterine pregnancy in September 2017 was treated with Methotrexate with no response and had surgical removal of right Fallopian tube. Choriocarcinoma was diagnosed one and a half year after extra uterine pregnancy. Radiological imaging before treatment showed pulmonary and inguinal lymph node metastases and tumor invasion of the anterior uterine wall. Surgery was performed due to heavy bleeding and uterine wall invasion. As high risk patient she received chemotherapy. She was followed radiologically and her serum ?-HCG was monitored. Refractivity to the chemotherapy protocol during treatment was observed. Therapy response was achieved after administration of EMA-EP protocol modification i.e. three consecutive negative follow-up values of ?-HCG were obtained and radiological findings were disease free. One month after treatment patient had no signs of disease and ?-HCG level was normal.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Adjuvant chemotherapy of resistant high risk choriocarcinoma

et al. 2021

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“…MTX-resistant JEG3/MTX and JAR/MTX sublines were established as we described previously. 13 The use of these choriocarcinoma cell lines in this study was approved by the institutional research ethics committee in Xiangya Hospital, Central South University. These cell lines were routinely grown in Dulbecco's Modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum.…”

Section: Reagents and Cell Linesmentioning

confidence: 99%

“…12 Recently, our quantitative proteomics analysis identified multiple genes/pathways potentially associated with chemoresistance to MTX in JEG3 choriocarcinoma cells, which still awaits functional validation. 13 Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1, CD150) belongs to signaling lymphocyte activation molecule (SLAM) family of cell-surface receptors in hematopoietic cells. 14 In hematologic malignancies, SLAMF1 expression is mainly expressed in cutaneous T-cell lymphomas, Hodgkin's lymphoma, chronic lymphocytic leukemia, and multiple myeloma.…”

Section: Introductionmentioning

confidence: 99%

“…20 However, the function of SLAMF1 in the regulation of MTX resistance still remains largely unknown. In our previous proteomics study, highly elevated expression of SLAMF1 was observed in MTX-resistant JEG3/MTX subline compared to parental JEG3, 13 which sparked our interest to investigate its function in the chemoresistance to MTX in choriocarcinoma.…”

Section: Introductionmentioning

confidence: 99%

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SLAMF1 Promotes Methotrexate Resistance via Activating Autophagy in Choriocarcinoma Cells

Shi¹,

Zhang²,

Tian³

2020

CMAR

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The acquisition of chemoresistance to methotrexate (MTX) still remains one of the major challenges for choriocarcinoma treatment. Herein, we aimed to evaluate the potential role of Signaling Lymphocytic Activation Molecule Family Member 1 (SLAMF1) as a possible regulator of chemoresistance to MTX in choriocarcinoma. Material and Methods: MTX-resistant JEG3 and JAR sublines (JEG3/MTX, JAR/MTX) were used to study SLAMF1 function. CCK8 assay and soft agar assay were conducted to measure the cell viability and clonogenesis of choriocarcinoma cells, respectively; MDC incorporation assay was conducted for the quantification of intracellular autophagy; BrdU labeling was used to assess the proliferative potential of choriocarcinoma cells; SLAMF1 protein expression was analyzed by Western blotting. Results: Upregulation of SLAMF1 expression was observed in MTX-resistant JEG3/MTX and JAR/MTX sublines compared to their parental JEG3 and JAR cell lines, respectively. Knockdown of SLAMF1 markedly attenuated cell viability and soft agar clonogenesis after incubation with MTX in JEG3/MTX and JAR/MTX cells. In contrast, constitutive expression of SLAMF1 rescued cell survival soft agar clonogenesis in JEG3 and JAR cells treated with MTX. Moreover, autophagy is apparently activated in MTX-resistant JEG3/MTX and JAR/MTX sublines compared to their parental cell lines. Autophagy inhibitor 3-methyladenine and bafilomycin A1 enhanced MTX-induced cytotoxicity in MTX-resistant JEG3 and JAR sublines. Further, SLAMF1 might activate autophagy-related mechanism to promote resistance to MTX in choriocarcinoma cells. Depletion of SLAMF1 suppressed autophagy and induced apoptosis in MTX-treated JEG3/MTX and JAR/MTX cells. Conclusion: SLAMF1 might promote MTX resistance via activating protective autophagy in choriocarcinoma cell lines. Targeting SLAMF1 might be a useful therapeutic strategy to sensitize choriocarcinoma cells to MTX-based regimens.

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Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance

Mitra

Hou

et al. 2023

Advanced Science

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Adenosine‐to‐inosine RNA editing critically affects the response of cancer therapies. However, comprehensive identification of drug resistance‐related RNA editing events and systematic understanding of how RNA editing mediates anticancer drug resistance remain unclear. Here, 7157 differential editing sites (DESs) are identified from 98 127 informative RNA editing sites in tumor tissues, many of which are validated in cancer cell lines. Diverse editing patterns of DESs are discovered in resistant samples, which could not be fully explained by adenosine deaminase acting on RNA enzymes. Some RNA‐binding proteins are identified that potentially regulate these editing events. Notably, the DESs are significantly enriched in 3’‐untranslated regions (3’‐UTRs). The impact of DESs in 3’‐UTR on the microRNA (miRNA) regulations is explored, and some triplets (DES, miRNA, and gene) that may contribute to drug resistance are identified. In addition, it is determined that the functions of genes enriched with DESs are associated with drug resistance, such as apoptosis, drug metabolism, and DNA synthesis involved in DNA repair. An online resource (http://www.jianglab.cn/REDR/) to support convenient retrieval of DESs is also built. The findings reveal the landscape and potential regulatory mechanism of RNA editing in drug resistance, providing new therapeutic targets for reversing drug resistance.

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Quantitative proteomic analysis identifies novel regulators of methotrexate resistance in choriocarcinoma

Cited by 36 publications

References 36 publications

Adjuvant chemotherapy of resistant high risk choriocarcinoma

Adjuvant chemotherapy of resistant high risk choriocarcinoma

SLAMF1 Promotes Methotrexate Resistance via Activating Autophagy in Choriocarcinoma Cells

Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance

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