Title:Guggulsterone Promotes Nasopharyngeal Carcinoma Cells Exosomal
Circfip1L1 to Mediate miR-125a-5p/VEGFA Affecting Tumor Angiogenesis
Volume: 16
Author(s): Ting Zhou, Shunli Zhao, Sanyuan Tang, Yongli Wang, Ruoxia Wu, Xiaoyan Zeng, Ping Yang, Xi Zhang*Xuefei Tian*
Affiliation:
- Clinical Medicine College, Hunan University of Traditional Chinese Medicine, Changsha, China
- Department of Oncology,
Brain Hospital of Hunan Province, Changsha, China
- Department of Internal Medicine, College
of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China
Keywords:
Guggulsterone, nasopharyngeal carcinoma, exosomal circFIP1L1, miR-125a-5p, VEGFA, angiogenesis.
Abstract:
Background: Nasopharyngeal carcinoma (NPC) is a usual head and neck malignancy. Guggulsterone
(GS) has potential in cancer chemoprophylaxis and treatment, but its therapeutic effect on
NPC is unknown. We aimed to explore whether GS could promote the secretion of exosomal circFIP1L1
from NPC cells and its regulatory mechanism.
Methods: NPC tissues and adjacent tissues were collected from NPC patients. Human nasopharyngeal
epithelial cell lines (NP69) and NPC lines (5-8F, CNE1, and HNE1) were used for in vitro experiments.
HNE1 cells were treated with GS (20, 40, 60 μmol/L). The expressions of miR-125a-5p and circFIP1L1
were evaluated by qRT-PCR. Cell proliferation and apoptosis abilities were measured by CCK-8 and
flow cytometry. HNE1 cell exosomes were extracted and identified, and the levels of VEGFA and
VEGFR2 were detected by ELISA. Then miR-125a-5p was knocked down and overexpressed. HUVECs
angiogenesis was determined by the tube formation assay. qRT-PCR and Western blot were utilized to
evaluate the expressions of VEGFA, MMP-2, MMP-9, and ICAM-1 in HUVECs.
Results: miR-125a-5p was highly expressed in NPC tissues and cells. GS promoted the secretion of
exosomal circFIP1L1 from HNE1 cells to affect HUVECs proliferation and angiogenesis. Overexpression
of miR-125a-5p accelerated HUVECs proliferation and angiogenesis. Knocking down miR-125a-
5p inhibited VEGFA expression. In addition, exosomal circFIP1L1 sponged miR-125a-5p, inhibiting
the VEGFA pathway to repress HUVECs angiogenesis.
Conclusions: GS promoted exosomal circFIP1L1 in NPC cells to mediate miR-125a-5p/VEGFA axis
affecting tumor angiogenesis.
