2. Academic Validation
  3. The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7

  • Cardiovasc Diabetol. 2024 Jan 9;23(1):21. doi: 10.1186/s12933-024-02119-z.
Wujun Chen # 1,  Xiaolin Wu # 1,  Jianxia Hu 2,  Xiaolei Liu 3,  Zhu Guo 1,  Jianfeng Wu 4,  Yingchun Shao 1,  Minglu Hao 1,  Shuangshuang Zhang 1,  Weichao Hu 1 5,  Yanhong Wang 1,  Miao Zhang 1,  Meng Zhu 1 6,  Chao Wang 7,  Yudong Wu 8,  Jie Wang 9,  Dongming Xing 10 11
Affiliations

Affiliations

  • 1 Cancer Institute, Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China.
  • 2 Department of Endocrinology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 3 Department of Gastrointestinal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 4 Department of Cardiology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Key Laboratory of Heart Failure Prevention & Treatment of Hengyang, Clinical Medicine Research Center of Arteriosclerotic Disease of Hunan Province, Hengyang, 421001, Hunan, China.
  • 5 Department of Endocrinology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, 266000, Shandong, China.
  • 6 Department of Neurosurgery, The Affiliated Hospital of Qingdao University, Qingdao, 266071, Shandong, China.
  • 7 Cancer Institute, Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. wangchao20086925@126.com.
  • 8 Cancer Institute, Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. 867969404@qq.com.
  • 9 Cancer Institute, Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. 1062639022@qq.com.
  • 10 Cancer Institute, Department of Orthopaedics, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, 266071, Shandong, China. xdm_tsinghua@163.com.
  • 11 School of Life Sciences, Tsinghua University, Beijing, 100084, China. xdm_tsinghua@163.com.
  • # Contributed equally.
PMID: 38195542 DOI: 10.1186/s12933-024-02119-z
Abstract

Atherosclerosis is one of the leading causes of death worldwide. miR-26 is a potential biomarker of atherosclerosis. Standardized diagnostic tests for miR-26 (MIR26-DX) have been developed, but the fastest progress has been in predicting the efficacy of IFN-α therapy for hepatocellular carcinoma (HCC, phase 3). MiR-26 slows atherosclerosis development by suppressing ACC1/2, ACLY, ACSL3/4, ALDH3A2, ALPL, BMP2, CD36, COL1A1, CPT1A, CTGF, DGAT2, EHHADH, FAS, FBP1, GATA4, GSK3β, G6PC, Gys2, HMGA1, HMGB1, LDLR, LIPC, IL-1β, IL-6, JAG2, KCNJ2, MALT1, β-MHC, NF-κB, PCK1, PLCβ1, PYGL, RUNX2, SCD1, SMAD1/4/5/7, SREBF1, TAB3, TAK1, TCF7L2, and TNF-α expression. Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants 68Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials. Interestingly, miR-26 better reduced intima-media thickness (IMT) than PCSK9 or CT-1 knockout. Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials. Recombinant CT-1 was also investigated in clinical trials. Therefore, miR-26 is a promising target for agent development. miR-26 promotes foam cell formation by reducing ABCA1 and ARL4C expression. Multiple Materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it.

Keywords

COL1A1; DGAT2; FBP1; IFN-α therapy; SMAD7; miR-26.

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