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Liang Deng,1,* Shan Huang,2,* Bin Chen,3 Yajun Tang,1 Fei Huang,1 Dong Li,1 Di Tang1 1Department of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 2Department of Oncology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong 518107, People’s Republic of China; 3Department of Hepatic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510800, People’s Republic of China*These authors contributed equally to this workCorrespondence: Di TangDepartment of General Surgery, The Seventh Affiliated Hospital of Sun Yat-sen University, No. 628 Zhenyuan Road, Xinhu Street, Guangming District, Shenzhen, Guangdong 518107, People’s Republic of ChinaTel +86 18929343913Email tangdi@126.comBackground: 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-M&phis;s) 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-M&phis;s and TAMs-M&phis;s but were suppressed by HMGA2 down-regulated HepG2 cells. In addition, TAMs-M&phis;s 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.Keywords: HMGA2, hepatocellular carcinoma, TAMs, LncRNA CCAT1, let-7b |
