Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer

Wu, Jingjing; Zhang, Shizhen; Shan, Jixiu; Hu, Zujian; Liu, Xiyong; Chen, Lirong; Ren, Xing-chang; Yao, Lifang; Sheng, Hongqiang; Li, Ling; Ann, David K.; Yen, Yun; Wang, Jian; Wang, Xiaochen

doi:10.1016/j.canlet.2016.04.005

Cited by 73 publications

(62 citation statements)

References 45 publications

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“…As a transcriptional factor, HMGA2 is increased in many malignant tumors such as lung cancer [41], ovarian cancer [42], and bladder cancer [43], which targets different downstream genes in the process of tumorigenesis [44][45][46]. Wu et al [47] proved that HMGA2 expression was positively correlated with tumor histological grade, and it was important with pathogenesis of breast cancer. Therefore, HMGA2 is becoming recognized as a key mediator in numerous mesenchymal and epithelial malignancies.…”

Section: Discussionmentioning

confidence: 99%

Retracted: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer

et al. 2018

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To study the regulatory effect of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on breast cancer (BC) cell growth, cell mobility, invasiveness, and apoptosis. The microarray data of lncRNAs and mRNAs with differential expression in BC tissues were analyzed in the Cancer Genome Atlas (TCGA) database. LncRNA HOX transcript antisense RNA (lncRNA HOTAIR) expression in BC was assessed by qRT‐PCR. Cell viability was confirmed using MTT and colony formation assay. Cell apoptosis was analyzed by TdT‐mediated dUTP nick‐end labeling (TUNEL) assay. Cell mobility and invasiveness were testified by transwell assay. RNA pull‐down and dual luciferase assay were used for analysis of the correlation between lncRNA HOTAIR and miR‐20a‐5p, as well as relationship of miR‐20a‐5p with high mobility group AT‐hook 2 (HMGA2). Tumor xenograft study was applied to confirm the correlation of lncRNA HOTAIR/miR‐20a‐5p/HMGA2 axis on BC development in vivo. The expression levels of the lncRNA HOTAIR were upregulated in BC tissues and cells. Knockdown lncRNA HOTAIR inhibited cell propagation and metastasis and facilitated cell apoptosis. MiR‐20a‐5p was a target of lncRNA HOTAIR and had a negative correlation with lncRNA HOTAIR. MiR‐20a‐5p overexpression in BC suppressed cell growth, mobility, and invasiveness and facilitated apoptosis. HMGA2 was a target of miR‐20a‐5p, which significantly induced carcinogenesis of BC. BC cells progression was mediated by lncRNA HOTAIR via affecting miR‐20a‐5p/HMGA2 in vivo. LncRNA HOTAIR affected cell growth, metastasis, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer.

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Section: Discussionmentioning

confidence: 99%

Retracted: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer

et al. 2018

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“…In the network presented herein, miR-9 directly targeted HMGA2, EGR1 and IGFBP3. These three coding RNAs are closely related to the invasion and metastasis of breast cancer [20, 26, 27]. The expression level of miR-210 in MDA-MB-231 cells is 4 times higher than that in MCF-7 cells in the present study.…”

Section: Discussionmentioning

confidence: 48%

Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines Revealed by Next Generation Sequencing

Shi

Peng

Long³

2017

Cell Physiol Biochem

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Background/Aims: As MCF-7 and MDA-MB-231 cells are the typical cell lines of two clinical breast tumour subtypes, the aim of the present study was to elucidate the transcriptome differences between MCF-7 and MDA-MB-231 breast cancer cell lines. Methods: The mRNA, miRNA (MicroRNA) and lncRNA (Long non-coding RNA) expression profiles were examined using NGS (next generation sequencing) instrument Illumina HiSeq-2500. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to identify the biological functions of differentially expressed coding RNAs. Subsequently, we constructed an mRNA-ncRNA (non-coding RNA) targeting regulatory network. Finally, we performed RT-qPCR (real-time quantitative PCR) to confirm the NGS results. Results: There are sharp distinctions of the coding and non-coding RNA profiles between MCF-7 and MDA-MB-231 cell lines. Among the mRNAs and ncRNAs with the most differential expression, SLPI, SOD2, miR-7, miR-143 and miR-145 were highly expressed in MCF-7 cells, while CD55, KRT17, miR-21, miR-10b, miR-9, NEAT1 and PICSAR were over-expressed in MDA-MB-231 cells. Differentially expressed mRNAs are primarily involved in biological processes of locomotion, biological adhesion, ECM-receptor interaction pathway and focal adhesion. In the targeting regulatory network of differentially expressed RNAs, mRNAs and miRNAs are primarily associated with tumour metastasis, but the functions of lncRNAs remain uncharacterized. Conclusion: These results provide a basis for future studies of breast cancer metastasis and drug resistance.

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“…High mobility group A2 (HMGA2), as an oncoprotein, plays a very important role in embryogenesis and tumorigenesis [3][4][5][6][7][8]. It is highly expressed in different cancers, whereas it is almost absent in terminally differentiated tissues [9,10].…”

Section: Introductionmentioning

confidence: 99%

HMGA2 promotes intestinal tumorigenesis by facilitating MDM2‐mediated ubiquitination and degradation of p53

Wang

et al. 2018

The Journal of Pathology

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High mobility group A2 (HMGA2) is an architectural transcription factor that promotes human colorectal cancer (CRC) aggressiveness by modulating the transcription of target genes. The degradation of p53 is mediated by murine double minute 2 (MDM2) in a proteasome-dependent manner. Here we report that HMGA2 promotes cell cycle progression and inhibits apoptosis in CRC cells in vitro. We also developed an intestinal epithelial cell-specific Hmga2 knock-in (KI) mouse model. It revealed that the Hmga2 KI promoted chemical carcinogen-induced tumorigenesis in the intestine in vivo. In studying the underlying molecular mechanism, we found that HMGA2 formed a protein complex with p53. The tetramerization domain of p53 (amino acids 294-393) and the three AT-hook domains (amino acids 1-83) of HMGA2 were responsible for their direct interaction. We also found that HMGA2 directly bound to MDM2 and the central acidic and zinc finger domains of MDM2 (amino acids 111-360) were required for interaction with HMGA2. Furthermore, our results indicated that HMGA2 promoted MDM2-mediated p53 ubiquitination and degradation. Interestingly, Hmga2 overexpression in Hmga2 KI mice resulted in an increase in the accumulation of ubiquitinated p53. In addition, in two large CRC cohorts, it was demonstrated that high HMGA2 expression was predictive of an adverse outcome in the p53-negative subgroup of CRC patients. In summary, our data have established for the first time a novel mechanism by which HMGA2 functions with p53 and MDM2 to promote CRC progression. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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Elevated HMGA2 expression is associated with cancer aggressiveness and predicts poor outcome in breast cancer

Cited by 73 publications

References 45 publications

Retracted: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer

Retracted: LncRNA HOTAIR influences cell growth, migration, invasion, and apoptosis via the miR‐20a‐5p/HMGA2 axis in breast cancer

Differential Expression Profiles of the Transcriptome in Breast Cancer Cell Lines Revealed by Next Generation Sequencing

HMGA2 promotes intestinal tumorigenesis by facilitating MDM2‐mediated ubiquitination and degradation of p53

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