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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Main Authors: Xiaotian Han, Yechen Lu, Xiaoqi Li, Lingfang Xia, Hao Wen, Zheng Feng, Xingzhu Ju, Xiaojun Chen, Xiaohua Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-03-01
Series:Frontiers in Oncology
Subjects:
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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