SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell.

Abstract

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a huge challenge. Copper transporter protein 1 (CTR1), a copper influx transporter required for high affinity copper (probably reduced Cu I) transport into the cell, reportedly promotes a significant fraction of DDP internalization in tumor cells. In the present study, we evaluated the function of CTR1 in the cell proliferation of cervical cancer upon DDP treatment. MicroRNAs (miRNAs) have been regarded as essential regulators of cell proliferation, apoptosis, migration, as well as chemoresistance. By using online tools, we screened for candidate miRNAs potentially regulate CTR1, among which miR-130a has been proved to promote cervical cancer cell proliferation through targeting PTEN in our previous study. In the present study, we investigated the role of miR-130a in cervical cancer chemoresistance to DDP, and confirmed the binding of miR-130a to CTR1. SOX9 also reportedly act on cancer chemoresistance. In the present study, we revealed that SOX9 inversely regulated miR-130a through direct targeting the promoter of miR-130a. Consistent with previous studies, SOX9 could affect cervical cancer chemoresistance to DDP. Taken together, we demonstrated a SOX9/miR-130a/CTR1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

• Authors: Chenzhe Feng, Fang Ma, Chunhong Hu, Jin-An Ma, Jingjing Wang, Yang Zhang, Fang Wu, Tao Hou, Shun Jiang, Yapeng Wang, Yeqian Feng
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 17 Issue 4 Pg. 448-458 ( 2018) ISSN: 1551-4005 [Electronic] United States
• PMID: 29099271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 3' Untranslated Regions
• Antagomirs
• Cation Transport Proteins
• Copper Transporter 1
• MIRN130 microRNA, human
• MicroRNAs
• RNA, Small Interfering
• SLC31A1 protein, human
• SOX9 Transcription Factor
• SOX9 protein, human
• PTEN Phosphohydrolase
• PTEN protein, human
• Cisplatin

Topics

• 3' Untranslated Regions
• Antagomirs (metabolism)
• Apoptosis (drug effects)
• Cation Transport Proteins (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Copper Transporter 1
• Drug Resistance, Neoplasm (drug effects)
• Female
• HeLa Cells
• Humans
• MicroRNAs (antagonists & inhibitors, genetics, metabolism)
• PTEN Phosphohydrolase (metabolism)
• Promoter Regions, Genetic
• Protein Binding
• RNA Interference
• RNA, Small Interfering (metabolism)
• SOX9 Transcription Factor (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction (drug effects)
• Uterine Cervical Neoplasms