Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia
BackgroundEpithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about...
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Frontiers Media S.A.
2021-03-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.643986/full |
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author | Xiaotian Han Xiaotian Han Yechen Lu Xiaoqi Li Xiaoqi Li Lingfang Xia Lingfang Xia Hao Wen Hao Wen Zheng Feng Zheng Feng Xingzhu Ju Xingzhu Ju Xiaojun Chen Xiaojun Chen Xiaohua Wu Xiaohua Wu |
author_facet | Xiaotian Han Xiaotian Han Yechen Lu Xiaoqi Li Xiaoqi Li Lingfang Xia Lingfang Xia Hao Wen Hao Wen Zheng Feng Zheng Feng Xingzhu Ju Xingzhu Ju Xiaojun Chen Xiaojun Chen Xiaohua Wu Xiaohua Wu |
author_sort | Xiaotian Han |
collection | DOAJ |
description | BackgroundEpithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.MethodsBioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.ResultsEOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment. NPTX2 knockdown abolished the hypoxia-induced malignant phenotypes in ECO.ConclusionsThe above results suggest that NPTX2 may play a novel role in ovarian cancer’s malignant phenotype and act as a promising treatment target for EOC molecular therapy. |
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spelling | doaj.art-82986329752e4271b2befa7b5e4e3c7e2022-12-21T23:26:27ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-03-011110.3389/fonc.2021.643986643986Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under HypoxiaXiaotian Han0Xiaotian Han1Yechen Lu2Xiaoqi Li3Xiaoqi Li4Lingfang Xia5Lingfang Xia6Hao Wen7Hao Wen8Zheng Feng9Zheng Feng10Xingzhu Ju11Xingzhu Ju12Xiaojun Chen13Xiaojun Chen14Xiaohua Wu15Xiaohua Wu16Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaWound Repair Center, Ruijin Hospital, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, ChinaDepartment of Oncology, Shanghai Medical College, Fudan University, Shanghai, ChinaBackgroundEpithelial ovarian cancer (EOC) is the main subtype of ovarian cancer and shows an aggressive phenotype and poor prognosis. Neuronal pentraxin II (NPTX2) is a member of the neuronal pentraxin family and plays a contradictory role in different tumors. However, there has been no report about the possible role and effect of NPTX2 in EOC.MethodsBioinformatics analysis, qPCR, western blotting and immunohistochemistry were used to detect the expression of NPTX2 in EOC. Lentivirus-based transfection for NPTX2 overexpression or knockdown was performed on the EOC cell lines A2780, HEY, SKOV3 and OVCAR-3. The effect of NPTX2 on the malignant phenotype of EOC was examined through methods of MTS assay, Edu assay, transwell assay, western blotting analysis, qPCR analysis, luciferase reporter assay and xenograft experiment.ResultsEOC tissues showed higher NPTX2 expression than the normal tissues with poor prognosis. NPTX2 overexpression can promote the proliferation, invasion, migration and tumorigenesis of EOC via IL6-JAK2/STAT3 signaling pathway. Moreover, hypoxia-inducible factor-1(HIF-1) can promote the transcription and expression of NPTX2 under the hypoxic environment. NPTX2 knockdown abolished the hypoxia-induced malignant phenotypes in ECO.ConclusionsThe above results suggest that NPTX2 may play a novel role in ovarian cancer’s malignant phenotype and act as a promising treatment target for EOC molecular therapy.https://www.frontiersin.org/articles/10.3389/fonc.2021.643986/fullNPTX2epithelial ovarian carcinoma (EOC)IL6-JAK2/STAT3 signaling pathwaymalignant phenotypehypoxia |
spellingShingle | Xiaotian Han Xiaotian Han Yechen Lu Xiaoqi Li Xiaoqi Li Lingfang Xia Lingfang Xia Hao Wen Hao Wen Zheng Feng Zheng Feng Xingzhu Ju Xingzhu Ju Xiaojun Chen Xiaojun Chen Xiaohua Wu Xiaohua Wu Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia Frontiers in Oncology NPTX2 epithelial ovarian carcinoma (EOC) IL6-JAK2/STAT3 signaling pathway malignant phenotype hypoxia |
title | Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia |
title_full | Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia |
title_fullStr | Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia |
title_full_unstemmed | Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia |
title_short | Overexpression of NPTX2 Promotes Malignant Phenotype of Epithelial Ovarian Carcinoma via IL6-JAK2/STAT3 Signaling Pathway Under Hypoxia |
title_sort | overexpression of nptx2 promotes malignant phenotype of epithelial ovarian carcinoma via il6 jak2 stat3 signaling pathway under hypoxia |
topic | NPTX2 epithelial ovarian carcinoma (EOC) IL6-JAK2/STAT3 signaling pathway malignant phenotype hypoxia |
url | https://www.frontiersin.org/articles/10.3389/fonc.2021.643986/full |
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