Huang Jun, Deng Xinpei, Chen Xuedong, Chang Zaoshang, Lu Quzhe, Tang Anliu, Liu Peng
College of Basic Medicine, Shaoyang University, Shaoyang, China.
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
J Oncol. 2022 Aug 23;2022:8035083. doi: 10.1155/2022/8035083. eCollection 2022.
Circular RNAs (circRNAs) regulate complex functional processes and play crucial roles in cancer development and progression. It was reported that circKIF4 regulates the progression of triple-negative breast cancer (TNBC). This study evaluates the role of circKIF4 in breast cancer distant metastasis and metabolic reprogramming.
RT-qPCR was performed to verify the expression of circKIF4A in breast cancer, liver metastatic tissues, and cell lines. The function of circKIF4A in metastasis was evaluated both in vitro and in vivo through a series of experiments, including cell migration and glucose intake experiments. Additionally, we conducted molecular experiments to clarify the regulatory role of circKIF4A. We then conducted a Luciferase reporter assay and an RNA immunoprecipitation assay to identify the molecular interactions between circKIF4A and miRNA.
circKIF4A was overexpressed in breast cancer cell lines and tissues, inhibiting its expression and suppressing breast cancer growth and metastasis. Interestingly, we observed that circKIF4A reprogrammed the glucose metabolism of breast cancer, and silencing circKIF4A greatly affected glucose uptake and lactate production in breast cancer cells. miR-335 can be sponged by circKIF4A, which affected the expression of ALDOA/OCT4 protein and regulated HK2/PKM2 expression.
This study demonstrated that the circKIF4A-miR-335-OCT4/ALDOA-HK2/PKM2 axis is critical to breast cancer metabolic reprogramming, indicating that this axis could be a novel therapeutic target for the treatment of liver metastasis of breast cancer.
环状RNA（circRNAs）调节复杂的功能过程，并在癌症的发生和发展中发挥关键作用。据报道，circKIF4调节三阴性乳腺癌（TNBC）的进展。本研究评估circKIF4在乳腺癌远处转移和代谢重编程中的作用。
采用RT-qPCR验证circKIF4A在乳腺癌、肝转移组织和细胞系中的表达。通过一系列实验，包括细胞迁移和葡萄糖摄取实验，在体外和体内评估circKIF4A在转移中的功能。此外，我们进行了分子实验以阐明circKIF4A的调控作用。然后我们进行了荧光素酶报告基因测定和RNA免疫沉淀测定，以鉴定circKIF4A与miRNA之间的分子相互作用。
circKIF4A在乳腺癌细胞系和组织中过表达，抑制其表达可抑制乳腺癌的生长和转移。有趣的是，我们观察到circKIF4A重塑了乳腺癌的葡萄糖代谢，沉默circKIF4A极大地影响了乳腺癌细胞中的葡萄糖摄取和乳酸生成。miR-335可被circKIF4A吸附，这影响了ALDOA/OCT4蛋白的表达并调节HK2/PKM2的表达。
本研究表明，circKIF4A-miR-335-OCT4/ALDOA-HK2/PKM2轴对乳腺癌代谢重编程至关重要，表明该轴可能是治疗乳腺癌肝转移的新治疗靶点。
