肾细胞癌（RCC）的早期诊断困难和转移倾向是其特点。对于晚期RCC，舒尼替尼靶向治疗是临床推荐的一线药物，而舒尼替尼治疗的主要挑战是适应性耐药性。因此，研究舒尼替尼耐药机制至关重要。在这项研究中，我们发现circPTPN12在RCC组织中高度表达，与较差的临床结果相关。circPTPN12可以促进RCC细胞的增殖、迁移、侵袭和舒尼替尼耐药性。在机制上，发现circPTPN12与hnRNPM形成复合物，参与mRNA加工的调节。circPTPN12与hnRNPM的结合增强了hnRNPM维持IL-6 mRNA稳定性的能力，进一步激活STAT3信号通路。该研究揭示了circPTPN12 / hnRNPM / IL-6 / STAT3轴促进了RCC的进展和舒尼替尼耐药性，可能是缓解RCC的舒尼替尼耐药性的有希望的治疗靶点。©2023年作者。

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.© 2023. The Author(s).