Protein tyrosine phosphatase PTPN3 promotes drug resistance and stem cell-like characteristics in ovarian cancer.
The current standard treatment for ovarian cancer is aggressive surgery followed by platinum-based combination chemotherapy. Recurrence and chemotherapeutic drug resistance are the two main factors that account for the high mortality of most ovarian cancers. Liposomal doxorubicin is primarily used for the treatment of ovarian cancer when the disease has progressed after platinum-based chemotherapy. However, relatively little is known about the genomic changes that contribute to both cisplatin and doxorubicin resistance in high-grade serous ovarian cancer (HGSC) under the selective pressure of chemotherapy. Here, we found that protein tyrosine phosphatase PTPN3 gene expression was substantially increased in both cisplatin and doxorubicin-resistant ovarian cancer cells. Silencing of PTPN3 restored sensitivity to cisplatin and doxorubicin in resistant ovarian cancer cells. Down-regulation of PTPN3 also inhibited cell cycle progression, migration, stemness in vitro and the tumorigenicity of resistant ovarian cancer cells in vivo. Meanwhile, the expression of PTPN3 was found to be regulated by miR-199 in resistant ovarian cancer cells. These findings suggest that PTPN3 promotes tumorigenicity, stemness and drug resistance in ovarian cancer, and thus is a potential therapeutic target for the treatment of ovarian cancer.
Department of Gynecology and Obstetrics, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Shuqin
S
Li
Department of Gynecology and Obstetrics, Nanjing Maternal and Children Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
Jian
J
Cao
Department of Pathology, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Wei
W
Zhang
Department of Pathology, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Fan
F
Zhang
Department of Gynecology and Obstetrics, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Guantai
G
Ni
Department of Gynecology and Obstetrics, Yijishan Hospital of Wannan Medical College, Wuhu, China.
Qian
Q
Luo
Department of Gynecology and Obstetrics, Xiaogan Central Hospital, Xiaogan, China.
Man
M
Wang
Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
Xiang
X
Tao
Department of Pathology, Yijishan Hospital of Wannan Medical College, Wuhu, China.|Department of Pathology, Sir Run Run Hospital &Nanjing Medical University, Nanjing, China.
Hongping
H
Xia
D020413:3' Untranslated Regions; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use; D001483:Base Sequence; D001665:Binding Sites; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3 / Q000502:physiology*; D034622:RNA Interference
D020413:3' Untranslated Regions; D000903:Antibiotics, Antineoplastic; D035683:MicroRNAs; C531408:mirn199 microRNA, human; D004317:Doxorubicin; C516656:PTPN3 protein, human; D054589:Protein Tyrosine Phosphatase, Non-Receptor Type 3; D002945:Cisplatin