Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway
Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our stu...
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doaj-2c79a8db0f15411db37a1ba8217b4cb72021-06-02T18:53:50ZengThe Company of BiologistsBiology Open2046-63902019-09-018910.1242/bio.043570043570Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathwayAihong Wang0Canhui Jin1Xiaoyu Tian2Ying Wang3Hongyu Li4 Department of Gynecologic and Obstetrics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China Department of Gastrointestinal Tumor Surgery, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China Department of Gynecologic and Obstetrics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China Department of Gynecologic and Obstetrics, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China Department of Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our study, we found that expression levels of HE4 in tissues, serum and urine in ovarian cancer were upregulated compared to healthy and benign groups. HE4 expression was elevated in ovarian cancer cells. Knockdown of HE4 dampened cell proliferation and Ki67 expression, as well as enhanced apoptosis, caspase-3 activity and cleaved-caspase-3 expression. In addition, HE4 downregulation repressed invasion and migration capabilities of ovarian cancer cells. Western blot analyses showed that knockdown of HE4 reduced the levels of matrix metalloproteinases (MMP-2 and MMP-9) and inhibited epithelial to mesenchymal transition (EMT) in ovarian cancer cells. In vivo animal experiments revealed that HE4 downregulation constrained the growth of xenograft tumor. Mechanism research showed that knockdown HE4 inhibited the activity of JAK/STAT3 pathway in vitro and in vivo. In conclusion, our findings reported that knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway, which provides valuable insights to contribute to develop novel HE4-targeted therapies.http://bio.biologists.org/content/8/9/bio043570Ovarian cancerHE4Cell growthMalignant progressionJAK/STAT3 pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aihong Wang Canhui Jin Xiaoyu Tian Ying Wang Hongyu Li |
spellingShingle |
Aihong Wang Canhui Jin Xiaoyu Tian Ying Wang Hongyu Li Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway Biology Open Ovarian cancer HE4 Cell growth Malignant progression JAK/STAT3 pathway |
author_facet |
Aihong Wang Canhui Jin Xiaoyu Tian Ying Wang Hongyu Li |
author_sort |
Aihong Wang |
title |
Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway |
title_short |
Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway |
title_full |
Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway |
title_fullStr |
Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway |
title_full_unstemmed |
Knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway |
title_sort |
knockdown of he4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the jak/stat3 pathway |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2019-09-01 |
description |
Human epididymis protein 4 (HE4) is well known to be a predictor of ovarian cancer clinically. HE4 is reported to play crucial roles in ovarian cancer progression and metastasis. The purpose of the present study was to explore its biological role and molecular mechanism in ovarian cancer. In our study, we found that expression levels of HE4 in tissues, serum and urine in ovarian cancer were upregulated compared to healthy and benign groups. HE4 expression was elevated in ovarian cancer cells. Knockdown of HE4 dampened cell proliferation and Ki67 expression, as well as enhanced apoptosis, caspase-3 activity and cleaved-caspase-3 expression. In addition, HE4 downregulation repressed invasion and migration capabilities of ovarian cancer cells. Western blot analyses showed that knockdown of HE4 reduced the levels of matrix metalloproteinases (MMP-2 and MMP-9) and inhibited epithelial to mesenchymal transition (EMT) in ovarian cancer cells. In vivo animal experiments revealed that HE4 downregulation constrained the growth of xenograft tumor. Mechanism research showed that knockdown HE4 inhibited the activity of JAK/STAT3 pathway in vitro and in vivo. In conclusion, our findings reported that knockdown of HE4 suppresses aggressive cell growth and malignant progression of ovarian cancer by inhibiting the JAK/STAT3 pathway, which provides valuable insights to contribute to develop novel HE4-targeted therapies. |
topic |
Ovarian cancer HE4 Cell growth Malignant progression JAK/STAT3 pathway |
url |
http://bio.biologists.org/content/8/9/bio043570 |
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