Fatty acid β-oxidation promotes breast cancer stemness and metastasis via the miRNA-328-3p-CPT1A pathway

  • Cancer Gene Ther. 2022 Mar;29(3-4):383-395. doi: 10.1038/s41417-021-00348-y.
Feng Zeng   #  1  2 ,  Mingkang Yao   #  3  4 ,  Yun Wang   #  1 ,  Wei Zheng   #  5 ,  Shengshan Liu  1 ,  Zeyu Hou  1 ,  Xiaoming Cheng  1 ,  Suhong Sun  1 ,  Taolang Li  1 ,  Hongyuan Zhao  1 ,  Yi Luo  1 ,  Jiang Li  6  7  8
Affiliations
  • 1. Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
  • 2. Thyroid and Breast Surgery, The second Affiliated Hospital of Zunyi Medical University, Intersection of Xinpu Avenue and Xinlong Avenue in Xinpu New District, Zunyi, Guizhou, China.
  • 3. Respiratory medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 4. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
  • 5. Zhongshan Medical College of Sun Yat-sen University, Guangzhou, China.
  • 6. Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China. [email protected].
  • 7. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. [email protected].
  • 8. Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. [email protected].
  • # Contributed equally.
PMID: 34045663 DOI: 10.1038/s41417-021-00348-y
Abstract

MicroRNAs (miRNA) have been shown to be associated with tumor diagnosis, prognosis, and therapeutic response. MiR-328-3p plays a significant role in breast Cancer growth; however, its actual function and how it modulates specific biological functions is poorly understood. Here, miR-328-3p was significantly downregulated in breast Cancer, especially in patients with metastasis. Mitochondrial carnitine palmitoyl transferase 1a (CPT1A) is a downstream target gene in the miR-328-3p-regulated pathway. Furthermore, the miR-328-3p/CPT1A/fatty acid β-oxidation/stemness axis was shown responsible for breast Cancer metastasis. Collectively, this study revealed that miR-328-3p is a potential therapeutic target for the treatment of breast Cancer patients with metastasis, and also a model for the miRNA-fatty acid β-oxidation-stemness axis, which may assist inunderstanding the Cancer stem cell signaling functions of miRNA.

Products