circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway

Yi Shou; Changjie Yue; Qi Wang; Jingchong Liu; Jiaju Xu; Qi Miao; Di Liu; Hongmei Yang; Yuenan Liu; Xiaoping Zhang

doi:10.1038/s41419-023-05717-z

circPTPN12 promotes the progression and sunitinib resistance of renal cancer via hnRNPM/IL-6/STAT3 pathway

Cell Death Dis. 2023 Mar 31;14(3):232. doi: 10.1038/s41419-023-05717-z.

Authors

Yi Shou^#^{1

2

3}, Changjie Yue^#^{1

2}, Qi Wang^#^{1

2}, Jingchong Liu^{1

2}, Jiaju Xu^{1

2}, Qi Miao^{1

2}, Di Liu^{1

2}, Hongmei Yang^{1

4}, Yuenan Liu^{5

6}, Xiaoping Zhang^{7

8}

Affiliations

¹ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
² Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
³ Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China.
⁴ Department of Pathogenic Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.
⁵ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liuwhuh@hust.edu.cn.
⁶ Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. liuwhuh@hust.edu.cn.
⁷ Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xzhang@hust.edu.cn.
⁸ Institute of Urologic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. xzhang@hust.edu.cn.

^# Contributed equally.

Abstract

Renal cell carcinoma (RCC) is characterized by the difficulties in early diagnosis and the propensity to metastases. For advanced RCC, sunitinib targeted therapy is the clinically recommended first-line drug and the major challenge of sunitinib treatment is adaptive resistance. Therefore, it is imperative to research the mechanisms underlying sunitinib resistance. In this study, we discovered that circPTPN12 was highly expressed in RCC tissues and was associated with poorer clinical outcomes. circPTPN12 could promote the proliferation, migration, invasion, and sunitinib resistance of RCC cells. Mechanistically, circPTPN12 was found to form a complex with hnRNPM, which was involved in the regulation of mRNA processing. The combination with circPTPN12 enhanced the ability of hnRNPM to maintain the stability of IL-6 mRNA and further activated the STAT3 signaling pathway. The study revealed that circPTPN12/hnRNPM/IL-6/STAT3 axis promoted RCC progression and sunitinib resistance, which might be a promising therapeutic target for relieving sunitinib resistance in RCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell* / drug therapy
Carcinoma, Renal Cell* / genetics
Carcinoma, Renal Cell* / pathology
Cell Line, Tumor
Drug Resistance, Neoplasm / genetics
Heterogeneous-Nuclear Ribonucleoprotein Group M
Humans
Interleukin-6 / genetics
Interleukin-6 / metabolism
Kidney Neoplasms* / drug therapy
Kidney Neoplasms* / genetics
Kidney Neoplasms* / pathology
STAT3 Transcription Factor / genetics
STAT3 Transcription Factor / metabolism
Sunitinib / pharmacology
Sunitinib / therapeutic use

Substances

Sunitinib
Interleukin-6
HNRNPM protein, human
Heterogeneous-Nuclear Ribonucleoprotein Group M
STAT3 protein, human
STAT3 Transcription Factor