Micro<scp>RNA</scp>‐9 exerts antitumor effects on hepatocellular carcinoma progression by targeting <scp>HMGA</scp>2

Xu, Xiangang; Zou, Haibo; Luo, Lanyun; Xiankui, Wang; Wang, Guan

doi:10.1002/2211-5463.12716

Cited by 17 publications

(14 citation statements)

References 62 publications

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“…12 HMGA2 is also known to be expressed abnormally in several gastrointestinal malignancies such as esophageal cancer, gastric carcinoma, pancreatic cancer, HCC, and so on. [13][14][15][16] Owing to the elevated expression of HMGA2 in several malignant tumors, this protein is regarded as a prospective novel target for treating such tumors. 17 Upregulation of HMGA2 in HCC tissues was first evidenced by Wu et al to be associated with HCC size, capsule invasion, and vascular invasion, and the overexpression of HMGA2 may act as an independent prognostic marker.…”

Section: Introductionmentioning

confidence: 99%

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

Deng¹,

Huang²,

Chen³

et al. 2020

OTT

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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.

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Section: Introductionmentioning

confidence: 99%

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

Deng¹,

Huang²,

Chen³

et al. 2020

OTT

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“…including miR-663a, miR-107, microRNA-337 and microRNA-9 could inhibit hepatocellular carcinoma progression through suppression of HMGA2 expression [38][39][40]. However, whether these lncRNAs or microRNAs could interact with EGF and have a synergistic effect in regulation of HMGA2 transcription needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

Liang

Niu

Wang

et al. 2020

Preprint

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Abstract Background High-mobility group protein A2 (HMGA2) is highly expressed in hepatocellular carcinoma cells and contributes to tumor metastasis and poor patient survival. However, the molecular mechanism of HMGA2 transcriptional regulation in hepatocellular carcinoma cells remains largely unclear. Methods Mouse model of lung metastasis was used to evaluate the effects of HMGA2 on hepatocellular carcinoma. DEN-induced rat model of hepatocellular carcinoma was used to measure the expression of HMGA2 and histone H3 acetylation. Immunohistochemistry was used to analyze the expression levels of HMGA2 in 39 matched HCC tissues and adjacent non-tumor tissues. Real-time PCR, Western blotting and Chromatin Immunoprecipitation assay were used to investigate the underlying mechanisms by which HMGA2 overexpression in hepatocellular carcinoma cells. Result Compared with adjacent non-tumour tissues, the expression of HMGA2 was significantly upregulated in human HCC tumor tissues. Moreover, We demonstrated that the expression HMGA2 was upregulated in HCC, and the elevated HMGA2 could promote tumor metastasis. Incubation HCC cells with Epidermal growth factor (EGF) could promote the expression of HMGA2 mRNA and protein. Knockdown of p300 can reverse EGF-induced HMGA2 expression and histone H3-K9 acetylation, while a phosphorylation-mimic p300 S1834D mutant can stimulate HMGA2 expression as well as H3-K9 acetylation in HCC cells. Furthermore, we identified p300-mediated H3-K9 acetylation participates in EGF-induced HMGA2 expression in HCC. In addition, the levels of H3-K9 acetylation positively correlated with the expression levels of HMGA2 in human HCC specimens. Conclusion p300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma.

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“…In addition to lncRNAs, microRNAs (miRNAs) also have a role as tumor suppressor genes. miR-21-5p [91], miRNA-214 [92], miRNA-9 [93], miRNA- 370 [94], miRNA-622 [95], miR-1247-5p [96], miR-154 [97], miR-195 [98,99], miR-31 [100], miR-30e [101] miR-504 [102] regulate FASLG, PDK2 and PHF6, HMGA2, PIM1, MAP4K4, Wnt3, ZEB2, YAP and AEG-1, HDAC2 and CDK2, JAK1-STAT3-vimentin signaling, and FZD7, respectively.…”

Section: Targets Of Gene Therapymentioning

confidence: 99%

Current Status of Gene Therapy in Hepatocellular Carcinoma

Reghupaty

Sarkar

2019

Cancers

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Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer related deaths world-wide. Liver transplantation, surgical resection, trans-arterial chemoembolization, and radio frequency ablation are effective strategies to treat early stage HCC. Unfortunately, HCC is usually diagnosed at an advanced stage and there are not many treatment options for late stage HCC. First-line therapy for late stage HCC includes sorafenib and lenvatinib. However, these treatments provide only an approximate three month increase in survival. Besides, they cannot specifically target cancer cells that lead to a wide array of side effects. Patients on these drugs develop resistance within a few months and have to rely on second-line therapy that includes regorafenib, pembrolizumab, nivolumab, and cabometyx. These disadvantages make gene therapy approach to treat HCC an attractive option. The two important questions that researchers have been trying to answer in the last 2–3 decades are what genes should be targeted and what delivery systems should be used. The objective of this review is to analyze the changing landscape of HCC gene therapy, with a focus on these two questions.

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MicroRNA‐9 exerts antitumor effects on hepatocellular carcinoma progression by targeting HMGA2

Cited by 17 publications

References 62 publications

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

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

P300-dependent acetylation of histone H3 is required for EGFR-mediated HMGA2 transcription in hepatocellular carcinoma

Current Status of Gene Therapy in Hepatocellular Carcinoma

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