<p>Tumor-Linked Macrophages Promote HCC Development by Mediating the CCAT1/Let-7b/HMGA2 Signaling Pathway</p>

Abstract

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.

Assessment of immune status of laryngeal squamous cell carcinoma can predict prognosis and guide treatment

“…In most tumors, macrophages have been shown to participate in tumor growth and development, with chronic in ammation and aggressive phenotypes. The macrophages are present in hepatocellular carcinoma, gastric cancer, pancreatic duct adenocarcinoma, and melanoma, and have a poor prognosis [59][60][61][62]. Our research results support these observations.…”

A Mutation-Related Long Noncoding RNA Signature of Genome Instability Predicts Immune Infiltration and Hepatocellular Carcinoma Prognosis

“…High density of IgM+ and CD27− isotype-switched memory B cells was correlated with better survival, which may offer novel therapeutic targets ( Zhang et al, 2019b ). Macrophages M0 could aggravate HCC development stimulated by the CCAT1/let-7b/HMGA2 pathway ( Deng et al, 2020 ). Similarly, tumor-associated neutrophils promoted HCC progression and could be identified as potential targets for HCC treatment ( Zhou et al, 2016 ; Peng et al, 2020 ).…”

Noncoding RNA-mediated macrophage and cancer cell crosstalk in hepatocellular carcinoma

“…Interestingly, in a Transwell coculture system, HMGA2 overexpression in HCC cells promoted TAM migration and IL-10 expression, while IL-12 was inhibited. 166 This indicates that a positive feedback signaling loop between TAMs enhances HCC progression by targeting CCAT1-Let-7-HMGA2 HCC macrophages, leading to TAM (M0 type) infiltration and HCC progression. 166 , 168 …”

“…Mechanistically, CCAT1 can act as a miRNA sponge of let-7, miR-30c-2-3p, or miR-181 to antagonize their functions, resulting in the derepression of miRNA targets, such as HMGA2, c-Myc, and ATG7. 166 , 167 , 168 Recently, it was reported that, when cocultured either with TAMs in a Transwell system or with TAM supernatant, the expression levels of CCAT1 and HMGA2 were increased, while the expression level of let-7 was decreased. In addition, HMGA2 expression in HCC tissues was confirmed to be positively associated with TAM markers (CD68, CD163, and CD204).…”