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Author:

Zhang, Ting (Zhang, Ting.) | Zhang, Yanan (Zhang, Yanan.) | Liu, Jie (Liu, Jie.) | Ma, Yan (Ma, Yan.) | Ye, Qinong (Ye, Qinong.) | Yan, Xinlong (Yan, Xinlong.) (Scholars:阎新龙) | Ding, Lihua (Ding, Lihua.)

Indexed by:

SCIE

Abstract:

Background Altered lipid metabolism is closely related to the occurrence and development of hepatocellular carcinoma (HCC). Carnitine palmitoyltransferase 1C (CPT1C) is a member of CPT1 family and plays a key role in cancer development and progression. However, how microRNAs (miRNAs) regulate CPT1C-mediated fatty acid transport and oxidation remains to be elucidated. Methods Oil Red O staining, mitochondrial, and lipid droplets immunofluorescence staining were used to detect the functions of miR-377-3p and CPT1C in fatty acid oxidation. Colocalization of palmitate and mitochondria was performed to investigate the function of miR-377-3p and CPT1C in fatty acid transport into mitochondria. Fatty acid oxidation (FAO) assay was used to detect the function of miR-377-3p and CPT1C in FAO. Cell proliferation, migration and invasion assays and animal experiments were used to evaluate the role of miR-377-3p/CPT1C axis in HCC progression in vitro and in vivo. Immunofluorescence staining was used to identify the clinical significance of miR-377-3p and CPT1C in HCC patients. Results MiR-377-3p inhibits CPT1C expression by targeting its 3'-untranslated region. Through repression of CPT1C, miR-377-3p suppresses fatty acid oxidation by preventing fatty acid from entering into mitochondria and decreasing ATP production in HCC cells. Inhibiting fatty acid oxidation abolishes the ability of miR-377-3p/CPT1C axis to regulate HCC proliferation, migration, invasion and metastasis in vitro and in vivo. In HCC patients, CPT1C is significantly upregulated, and miR-377-3p expression and lipid droplets are negatively correlated with CPT1C expression. High expression of miR-377-3p and CPT1C predict better and worse clinical outcomes, respectively. Conclusions We uncover the key function and the relevant mechanisms of the miR-377-3p/CPT1C axis in HCC, which might provide a potential target for the treatment of HCC.

Keyword:

Fatty acid oxidation Tumor growth CPT1C miR-377-3p Metastasis Hepatocellular carcinoma

Author Community:

  • [ 1 ] [Zhang, Ting]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 2 ] [Zhang, Yanan]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 3 ] [Liu, Jie]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 4 ] [Ma, Yan]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 5 ] [Ye, Qinong]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 6 ] [Ding, Lihua]Beijing Inst Biotechnol, Dept Med Mol Biol, Beijing, Peoples R China
  • [ 7 ] [Zhang, Ting]Beijing Univ Technol, Fac Environm & Life, Beijing, Peoples R China
  • [ 8 ] [Yan, Xinlong]Beijing Univ Technol, Fac Environm & Life, Beijing, Peoples R China
  • [ 9 ] [Zhang, Yanan]Beijing Inst Basic Med Sci, Brain Sci Ctr, Beijing, Peoples R China
  • [ 10 ] [Ma, Yan]970 Hosp Joint Logist Support Force PLA, Yantai, Peoples R China

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Source :

CANCER & METABOLISM

Year: 2022

Issue: 1

Volume: 10

5 . 9

JCR@2022

5 . 9 0 0

JCR@2022

JCR Journal Grade:1

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count: 23

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 3

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