Wang Aihong, Jin Canhui, Tian Xiaoyu, Wang Ying, Li Hongyu
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.
Biol Open. 2019 Sep 2;8(9):bio043570. doi: 10.1242/bio.043570.
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. 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 and 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.
人附睾蛋白4（HE4）在临床上是众所周知的卵巢癌预测指标。据报道，HE4在卵巢癌的进展和转移中起关键作用。本研究的目的是探讨其在卵巢癌中的生物学作用和分子机制。在我们的研究中，我们发现与健康组和良性组相比，卵巢癌组织、血清和尿液中HE4的表达水平上调。HE4在卵巢癌细胞中表达升高。敲低HE4可抑制细胞增殖和Ki67表达，并增强细胞凋亡、caspase-3活性和裂解的caspase-3表达。此外，HE4下调可抑制卵巢癌细胞的侵袭和迁移能力。蛋白质印迹分析表明，敲低HE4可降低基质金属蛋白酶（MMP-2和MMP-9）的水平，并抑制卵巢癌细胞中的上皮-间质转化（EMT）。动物实验表明，HE4下调可抑制异种移植肿瘤的生长。机制研究表明，敲低HE4可抑制JAK/STAT3信号通路的活性。总之，我们的研究结果表明，敲低HE4通过抑制JAK/STAT3信号通路抑制卵巢癌细胞的侵袭性生长和恶性进展，这为开发新的HE4靶向治疗提供了有价值的见解。
