PMID- 38496248
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240319
IS  - 2253-5969 (Print)
IS  - 2253-5969 (Electronic)
IS  - 2253-5969 (Linking)
VI  - 11
DP  - 2024
TI  - LncRNA MEG3 Reduces the Ratio of M2/M1 Macrophages Through the HuR/CCL5 Axis in 
      Hepatocellular Carcinoma.
PG  - 543-562
LID - 10.2147/JHC.S449090 [doi]
AB  - OBJECTIVE: Tumor-associated macrophages play a crucial role in the development of 
      hepatocellular carcinoma (HCC). Our study aimed to investigate the relationship 
      between long coding RNA (lncRNA) maternally expressed gene 3 (MEG3), RNA-binding 
      protein human antigen R (HuR), and messenger RNA C-C motif chemokine 5 (CCL5) in 
      the modulation of M1 and M2 macrophage polarization in HCC. METHODS: To induce M1 
      or M2 polarization, LPS/IFNgamma- or IL4/IL13 were used to treat bone marrow derived 
      macrophages (BMDMs). The localization of MEG3 in M1 and M2 macrophages was 
      assessed using fluorescence in situ hybridization assay. Expression levels of 
      MEG3, HuR, CCL5, M1, and M2 markers were measured by RT-qPCR or 
      immunofluorescence staining. Flow cytometry was performed to determine the 
      proportion of F4/80+CD206+ and F4/80+CD68+ cells. RNA pulldown assay was 
      performed to detect the binding of lncRNA MEG3 and HuR. The impacts of HuR on 
      CCL5 stability and activity of CCL5 promoter were evaluated using actinomycin D 
      treatment and luciferase reporter assay. Cell migration, invasiveness, and 
      angiogenesis were assessed using transwell migration and invasion assays and a 
      tube formation assay. A mixture of Huh-7 cells and macrophages were injected into 
      nude mice to explore the effect of MEG3 on tumorigenesis. RESULTS: MEG3 promoted 
      M1-like polarization while dampening M2-like polarization of BMDMs. MEG3 bound to 
      HuR in M1 and M2 macrophages. HuR downregulated CCL5 by inhibiting CCL5 
      transcription in macrophages. In addition, overexpression of MEG3 suppressed cell 
      metastasis, invasion, and angiogenesis by obstructing macrophage M2 polarization. 
      MEG3 inhibited tumorigenesis in HCC via promotion of M1-like polarization and 
      inhibition of M2-like polarization. Rescue experiments showed that depletion of 
      CCL5 in M2 macrophages reversed MEG3-induced suppressive effect on cell 
      migration, invasion, and tube formation. CONCLUSION: MEG3 suppresses HCC 
      progression by promoting M1-like while inhibiting M2-like macrophage polarization 
      via binding to HuR and thus upregulating CCL5.
CI  - (c) 2024 Wei et al.
FAU - Wei, Huamei
AU  - Wei H
AD  - Department of Pathology, Affiliated Hospital of Youjiang Medical University for 
      Nationalities, Baise, Guangxi, People's Republic of China.
FAU - Wu, Xianjian
AU  - Wu X
AD  - Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical 
      University for Nationalities, Baise, Guangxi, People's Republic of China.
FAU - Huang, Lizheng
AU  - Huang L
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, People's Republic of China.
FAU - Long, Chen
AU  - Long C
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, People's Republic of China.
FAU - Lu, Qi
AU  - Lu Q
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, People's Republic of China.
FAU - Huang, Zheng
AU  - Huang Z
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, People's Republic of China.
FAU - Huang, Yanyan
AU  - Huang Y
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, People's Republic of China.
FAU - Li, Wenchuan
AU  - Li W
AD  - Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical 
      University for Nationalities, Baise, Guangxi, People's Republic of China.
FAU - Pu, Jian
AU  - Pu J
AD  - Department of Hepatobiliary Surgery, Affiliated Hospital of Youjiang Medical 
      University for Nationalities, Baise, Guangxi, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20240311
PL  - New Zealand
TA  - J Hepatocell Carcinoma
JT  - Journal of hepatocellular carcinoma
JID - 101674775
PMC - PMC10943271
OTO - NOTNLM
OT  - C-C motif chemokine 5
OT  - hepatocellular carcinoma
OT  - human antigen R
OT  - macrophage polarization
OT  - maternally expressed gene 3
COIS- The authors report no conflicts of interest in this work.
EDAT- 2024/03/18 06:42
MHDA- 2024/03/18 06:43
PMCR- 2024/03/11
CRDT- 2024/03/18 04:34
PHST- 2023/11/09 00:00 [received]
PHST- 2024/02/07 00:00 [accepted]
PHST- 2024/03/18 06:43 [medline]
PHST- 2024/03/18 06:42 [pubmed]
PHST- 2024/03/18 04:34 [entrez]
PHST- 2024/03/11 00:00 [pmc-release]
AID - 449090 [pii]
AID - 10.2147/JHC.S449090 [doi]
PST - epublish
SO  - J Hepatocell Carcinoma. 2024 Mar 11;11:543-562. doi: 10.2147/JHC.S449090. 
      eCollection 2024.