PMID- 37435155
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230718
IS  - 2253-5969 (Print)
IS  - 2253-5969 (Electronic)
IS  - 2253-5969 (Linking)
VI  - 10
DP  - 2023
TI  - LncRNA MEG3 Inhibits Tumor Progression by Modulating Macrophage Phenotypic 
      Polarization via miR-145-5p/DAB2 Axis in Hepatocellular Carcinoma.
PG  - 1019-1035
LID - 10.2147/JHC.S408800 [doi]
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is the predominant histological type 
      of primary liver cancer, which ranks sixth among the most common human tumors. 
      Tumor-associated macrophages (TAMs) are an important component of tumor 
      microenvironment (TME) and the M2 macrophage polarization substantially 
      contributes to tumor growth and metastasis. Long non-coding RNA (lncRNA) MEG3 was 
      reported to restrain HCC development. However, whether MEG3 regulates macrophage 
      phenotypic polarization in HCC remains unclear. METHODS: Bone marrow derived 
      macrophages (BMDMs) were treated with LPS/IFNgamma and IL4/IL13 to induce the M1 and 
      M2 macrophage polarization, respectively. M2-polarized BMDMs were simultaneously 
      transfected with adenovirus vector overexpressing MEG3 (Adv-MEG3). Subsequently, 
      M2-polarized BMDMs were cultured for 24 h with serum-free medium, the 
      supernatants of which were harvested as conditioned medium (CM). HCC cell line 
      Huh7 was cultured with CM for 24 h. F4/80(+)CD68(+) and F4/80(+)CD206(+) cell 
      percentages in M1-and M2-polarized BMDMs were calculated using flow cytometry. 
      Huh7 cell migration, invasion and angiogenesis were determined via Transwell 
      assay and tube formation experiment. Nude mice were implanted with Huh7 cells and 
      Adv-MEG3-transfected M2-polarizd BMDMs, and tumor growth and M2 macrophage 
      polarization markers were assessed. The binding between miR-145-5p and MEG3 or 
      disabled-2 (DAB2) was verified by luciferase reporter assay. RESULTS: MEG3 
      presented lower expression in HCC tissues than in normal controls, and low 
      expression of MEG3 was correlated to poorer prognosis of HCC patients. MEG3 
      expression was enhanced during LPS/IFNgamma-induced M1 polarization, but was reduced 
      during IL4/IL13-induced M2 polarization. MEG3 overexpression inhibited the 
      expression of M2 polarization markers in both M2-polarized BMDMs and mice. 
      Mechanically, MEG3 bound with miR-145-5p to regulate DAB2 expression. 
      Overexpressing MEG3 suppressed M2 polarization-induced HCC cell metastasis and 
      angiogenesis by upregulating DAB2 and inhibited in vivo tumor growth. CONCLUSION: 
      LncRNA MEG3 curbs HCC development by repressing M2 macrophage polarization via 
      miR-145-5p/DAB2 axis.
CI  - (c) 2023 Wei et al.
FAU - Wei, Qing
AU  - Wei Q
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, People's Republic of China.
FAU - Liu, Guoman
AU  - Liu G
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, People's Republic of China.
FAU - Huang, Zihua
AU  - Huang Z
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, People's Republic of China.
FAU - Huang, Yanyan
AU  - Huang Y
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, People's Republic of China.
FAU - Huang, Lizheng
AU  - Huang L
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, People's Republic of China.
FAU - Huang, Zheng
AU  - Huang Z
AD  - Graduate College of Youjiang Medical University for Nationalities, Baise, 
      Guangxi, 533099, 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, 533000, People's Republic of China.
FAU - Wei, Huamei
AU  - Wei H
AD  - Department of Pathology, Affiliated Hospital of Youjiang Medical University for 
      Nationalities, Baise, Guangxi, 533000, 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, 533000, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20230705
PL  - New Zealand
TA  - J Hepatocell Carcinoma
JT  - Journal of hepatocellular carcinoma
JID - 101674775
PMC - PMC10329916
OTO - NOTNLM
OT  - DAB2
OT  - MEG3
OT  - hepatocellular carcinoma
OT  - macrophage polarization
OT  - metastasis
OT  - miR-145-5p
OT  - tumor microenvironment
COIS- The authors declare no conflicts of interest in this work.
EDAT- 2023/07/12 06:42
MHDA- 2023/07/12 06:43
PMCR- 2023/07/05
CRDT- 2023/07/12 03:54
PHST- 2023/02/16 00:00 [received]
PHST- 2023/06/26 00:00 [accepted]
PHST- 2023/07/12 06:43 [medline]
PHST- 2023/07/12 06:42 [pubmed]
PHST- 2023/07/12 03:54 [entrez]
PHST- 2023/07/05 00:00 [pmc-release]
AID - 408800 [pii]
AID - 10.2147/JHC.S408800 [doi]
PST - epublish
SO  - J Hepatocell Carcinoma. 2023 Jul 5;10:1019-1035. doi: 10.2147/JHC.S408800. 
      eCollection 2023.