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Published on: March 17, 2023
Exogenous Kisspeptin-10 inhibits ovarian cancer progression through targeting the SP1-hTERT-ZEB1 regulatory axis
Hetvi Shah1, Abin Thomas2, Parth Pandya1
1TREE Lab, Division of Biomedical and Life Sciences, School of Science, Navrachana University, Vadodara, Gujarat India.
Abstract:
Ovarian cancer is one of the deadliest female gynaecological cancers, known to have high metastatic ability and telomerase reactivation. The current study aims to explore the influence of exogenous Kisspeptin-10 (KP-10) on the SP1-ZEB1-hTERT pathway in SKOV-3 ovarian cancer cell lines using both in vitro and computational techniques. KP-10 significantly inhibited SKOV-3 proliferation, migration, and invasion at a dose-dependent level with an IC₅₀ of 72.28 nM. The molecular mechanisms showed the ability of KP-10 to affect the regulation of important transcriptional factors such as SP1, CDX2, GATA2, FLI1, and ZEB1 and hTERT expression, indicating telomerase-related oncogenic signaling modulation. Besides, KP-10 influenced the expression of tumor suppressive microRNAs, including miR-200, miR-345, and miR-577 which are known to inhibit epithelial-mesenchymal transition, invasion, and development of cancer. The bioinformatics analysis of the KISS1 promoter showed multiple binding sites of SP1, CDX2, GATA2, FLI1, among others, indicating the transcription network in KISS1 regulation. Taken together, this paper shows the KP-10-mediated modulation of transcriptional factors involved in the SP1-ZEB1-hTERT pathway, inhibiting proliferative and metastatic phenotypes of ovarian cancer cells.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10616-026-01005-8.
Insights
Kisspeptin-10 (KP-10) effectively inhibits ovarian cancer cell growth and metastasis by targeting the SP1-ZEB1-hTERT pathway. This study reveals KP-10
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ovarian cancer is a leading cause of gynecological cancer deaths, characterized by high metastatic potential and telomerase reactivation.
- The SP1-ZEB1-hTERT pathway plays a crucial role in ovarian cancer progression and metastasis.
Purpose of the Study:
- To investigate the effects of exogenous Kisspeptin-10 (KP-10) on the SP1-ZEB1-hTERT pathway in SKOV-3 ovarian cancer cells.
- To elucidate the molecular mechanisms underlying KP-10's anti-cancer activity.
Main Methods:
- In vitro experiments using SKOV-3 ovarian cancer cell lines.
- Computational techniques including bioinformatics analysis of the KISS1 promoter.
- Assays to measure cell proliferation, migration, invasion, and gene/microRNA expression.
Main Results:
- KP-10 significantly inhibited SKOV-3 cell proliferation, migration, and invasion in a dose-dependent manner (IC₅₀ = 72.28 nM).
- KP-10 modulated the expression of key transcriptional factors (SP1, CDX2, GATA2, FLI1, ZEB1) and hTERT, indicating telomerase pathway interference.
- KP-10 influenced tumor-suppressive microRNAs (miR-200, miR-345, miR-577), known inhibitors of epithelial-mesenchymal transition and cancer development.
Conclusions:
- KP-10 effectively suppresses ovarian cancer cell proliferation and metastasis.
- KP-10 exerts its anti-cancer effects by modulating the SP1-ZEB1-hTERT pathway and associated transcriptional factors and microRNAs.
- These findings highlight KP-10 as a potential therapeutic agent for ovarian cancer.
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