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Published on: September 12, 2019
Tumor-Linked Macrophages Promote HCC Development by Mediating the CCAT1/Let-7b/HMGA2 Signaling Pathway
Liang Deng1, Shan Huang2, Bin Chen3
1Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, People's Republic of China.
Background:
The role of high mobility group A2 (HMGA2) in the progression of hepatocellular carcinoma (HCC) is yet to be investigated, though tumor-associated macrophages (TAMs) are known to mediate the process.
Methods:
Immunohistochemistry (IHC), Western blot, and real-time PCR assays were performed to identify HMGA2 and TAMs markers. The TAMs-like macrophages (TAMs-Mφs) were triggered with the help of 25 ng/mL hM-CSF and 50% NBCM. EdU assay wound healing assay, transwell assay, and TUNEL assay, as well as flow cytometry, were carried out to study the effect of HMGA2 or TAMs on the functioning of HCC cells.
Results:
HCC tumor tissues were detected with upregulated HMGA2 and TAMs markers (CD68, CD163, and CD204); in addition, HMGA2 was positively correlated with TAMs markers. The proliferation, migration, and invasion of HepG2 cells were also observed to be stimulated by HMGA2. Remarkably, cell apoptosis was not affected by upregulated HMGA2, but HMAG2 inhibition was observed to intensify it. Also, the release of CSF1 was observed to be amplified by HMGA2. HMGA2-overexpressed-HepG2 cells promoted the migrating abilities of both M0-Mφs and TAMs-Mφs but were suppressed by HMGA2 down-regulated HepG2 cells. In addition, TAMs-Mφs supernatant regulated the CCAT1/let-7b/HMGA2 signaling pathway by intensifying the malignant biological behaviors.
Conclusion:
HMGA2 stimulated TAMs-induced HCC progression, mediated by the CCAT1/let-7b/HMGA2 signaling pathway, TAMs aggravated HCC development.
Insights
High mobility group A2 (HMGA2) promotes hepatocellular carcinoma (HCC) progression by stimulating tumor-associated macrophages (TAMs). This interaction, mediated by the CCAT1/let-7b/HMGA2 pathway, exacerbates HCC development.
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- The role of High Mobility Group A2 (HMGA2) in hepatocellular carcinoma (HCC) progression remains under investigation.
- Tumor-associated macrophages (TAMs) are known to mediate HCC progression.
Purpose of the Study:
- To investigate the role of HMGA2 in HCC progression.
- To explore the interplay between HMGA2 and TAMs in HCC.
Main Methods:
- Immunohistochemistry (IHC), Western blot, and real-time PCR were used to detect HMGA2 and TAMs markers.
- Functional assays including EdU, wound healing, transwell, TUNEL, and flow cytometry were performed.
- TAMs-like macrophages (TAMs-Mφs) were generated and co-cultured with HCC cells.
Main Results:
- Upregulated HMGA2 and TAMs markers (CD68, CD163, CD204) were found in HCC tissues, with HMGA2 positively correlated with TAMs markers.
- HMGA2 enhanced proliferation, migration, and invasion of HepG2 cells, while HMGA2 inhibition increased apoptosis.
- HMGA2-overexpressing HCC cells promoted macrophage migration, and TAMs-Mφs supernatant modulated the CCAT1/let-7b/HMGA2 pathway.
Conclusions:
- HMGA2 stimulates TAMs-induced HCC progression.
- The CCAT1/let-7b/HMGA2 signaling pathway mediates HMGA2's role in HCC.
- TAMs aggravate HCC development, highlighting a critical interaction with HMGA2.
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