Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells

Xia, Yun; Li, Yin; Jiang, Ning; Guo, Wenjie; Tian, Haijun; Jiang, Xuesong; Wu, Jing; Chen, Meng; Wu, Jianzhong; He, Xia

doi:10.1016/j.bbrc.2015.05.068

Cited by 30 publications

(24 citation statements)

References 36 publications

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“…The important role of HMGA2 in stabilizing RFs implies that a knockdown of HMGA2 in cells would have a significant effect on their cell viability. This was evidenced for HEK293T cells used in this study, which is consistent with previous studies on prostate cancer PC3 cells (61), nasopharyngeal cancer cells (62), and breast adenocarcinoma (MDA-MB-468) cells (63) in which a decrease in cell viability upon HMGA2 knockdown was observed. We observed that after 96 h, the effect on cell viability was negligible and cells recovered as they reached confluency.…”

Section: Discussionsupporting

confidence: 92%

Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork

Krahn

Meier

et al. 2017

Biophysical Journal

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High mobility group AT-hook 2 (HMGA2) protein is composed of three AT-hook domains. HMGA2 expresses at high levels in both embryonic stem cells and cancer cells, where it interacts with and stabilizes replication forks (RFs), resulting in elevated cell proliferation rates. In this study, we demonstrated that HMGA2 knockdown reduces cell proliferation. To understand the features required for interaction between HMGA2 and RFs, we studied the solution structure of HMGA2, free and in complex with RFs, using an integrated host of biophysical techniques. Circular dichroism and NMR experiments confirmed the disordered state of unbound HMGA2. Dynamic light scattering and sedimentation velocity experiments demonstrated that HMGA2 and RF are monodisperse in solution, and form an equimolar complex. Small-angle x-ray scattering studies revealed that HMGA2 binds in a side-by-side orientation to RF where 3 AT-hooks act as a clamp to wrap around a distorted RF. Thus, our data provide insights into how HMGA2 interacts with stalled RFs and the function of the process.

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Section: Discussionsupporting

confidence: 92%

Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork

Krahn

Meier

et al. 2017

Biophysical Journal

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“…[21][22][23][24][25][26] In other malignancies, such as nasopharyngeal carcinoma, high HMGA2 expression is correlated with N stage, 2-year metastasis status and poor survival prognosis. 27,28 The correlation between HIT000218960 expression and clinicopathological features observed in our study was consistent with that of HMGA2. Taken together, these findings indicate that HIT000218960 plays its tumor promoting function via upregulation of HMGA2.…”

Section: Discussionsupporting

confidence: 87%

Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene

Yang

et al. 2016

Cell Cycle

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Accumulating evidence suggests that long noncoding RNAs (lncRNAs) play an important role in oncogenesis and tumor progression. However, our knowledge of lncRNAs in thyroid cancer is still limited. To explore the crucial lncRNAs involved in oncogenesis of papillary thyroid cancer (PTC), we acquired data of differentially expressed lncRNAs between PTC tissues and paired adjacent noncancerous thyroid tissues through lncRNA microarray. In the microarray data, we observed that a newly identified lncRNA, HIT000218960, was significantly upregulated in PTC tissues and associated with a well-known oncogene, high mobility group AT-hook 2 (HMGA2) gene. Both in normal thyroid tissues and PTC tissues, the expression of HIT000218960 was significantly positively correlated with that of HMGA2 mRNA. Knockdown of HIT000218960 in PTC cells resulted in downregulation of HMGA2. In addition, functional assays indicated that inhibition of HIT000218960 in PTC cells suppressed cell proliferation, colony formation, migration and invasion in vitro. Increased HIT000218960 expression in PTC tissues was obviously correlated with lymph node metastasis and multifocality, as well as TNM stage. Those findings suggest that HIT000218960 might acts as a tumor promoter through regulating the expression of HMGA2.

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“…Previous studies have reported a strong correlation between HMGA2 expression and tumor cell invasiveness 27–29. The ectopic expression of HMGA2 in epithelial cells induces epithelial-mesenchymal transition (EMT), which has been implicated in the acquisition of metastatic characteristics in tumor cells 30.…”

Section: Discussionmentioning

confidence: 99%

High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

Na¹,

Si²,

Huang³

et al. 2016

OTT

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High-mobility group AT-hook 2 (HMGA2) is involved in a wide spectrum of biological processes and is upregulated in several tumors, but its role in renal carcinoma remains unclear. The aim of this study was to examine the expression of HMGA2 and its relationship to the overall survival (OS) of patients with non-metastatic clear cell renal cell carcinoma (ccRCC) following surgery. The expression of HMGA2 was evaluated retrospectively by immunohistochemistry (IHC) in 162 patients with ccRCC who underwent nephrectomy in 2003 and 2004. An IHC analysis revealed that HMGA2 was expressed in the nuclei of tumor cells in 146 (90.1%) patients with ccRCC. The level of HMGA2 was positively correlated with tumor size, lymph node metastasis, and Fuhrman Grade. A Kaplan–Meier analysis with log-rank test found that patients with high HMGA2 expression had a poor outcome and that patients with low HMGA2 expression had better survival. Cox regression analysis showed that HMGA2 expression could serve as an independent prognostic factor for ccRCC patients. The efficacy of the following prognostic models was improved when HMGA2 expression was added: tumor node metastasis stage, UCLA Integrated Scoring System, Mayo Clinic stage, size, grade, and necrosis score. In summary, this study showed that HMGA2 expression is an independent prognostic factor for OS in patients with ccRCC. HMGA2 was found to be a valuable biomarker for ccRCC progression.

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Downregulating HMGA2 attenuates epithelial-mesenchymal transition-induced invasion and migration in nasopharyngeal cancer cells

Cited by 30 publications

References 36 publications

Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork

Nanoscale Assembly of High-Mobility Group AT-Hook 2 Protein with DNA Replication Fork

Long noncoding RNA HIT000218960 promotes papillary thyroid cancer oncogenesis and tumor progression by upregulating the expression of high mobility group AT-hook 2 (HMGA2) gene

High expression of HMGA2 predicts poor survival in patients with clear cell renal cell carcinoma

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