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

Krahn, Natalie; Meier, Markus; To, Vu; Booy, Evan P.; McEleney, Kevin; O'Neil, Joe D. J.; McKenna, Sean Andrew; Patel, Trushar R.; Stetefeld, Jörg

doi:10.1016/j.bpj.2017.10.026

Cited by 17 publications

(17 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SAXS is an excellent complementary structural-biophysical method, which enables solution structural studies of RNA, proteins, and their complexes, albeit at low-resolution [34,46,49,57,[63][64][65]. Solution X-ray scattering is employed for biological systems where obtaining high-quality crystals or labeling of biomolecules presents challenges [22,30,31,49,63,64].…”

Section: Discussionmentioning

confidence: 99%

Nanoscale Structure Determination of Murray Valley Encephalitis and Powassan Virus Non-Coding RNAs

Mrozowich

Henrickson

Demeler

et al. 2020

Viruses

View full text Add to dashboard Cite

Viral infections are responsible for numerous deaths worldwide. Flaviviruses, which contain RNA as their genetic material, are one of the most pathogenic families of viruses. There is an increasing amount of evidence suggesting that their 5' and 3' non-coding terminal regions are critical for their survival. Information on their structural features is essential to gain detailed insights into their functions and interactions with host proteins. In this study, the 5' and 3' terminal regions of Murray Valley encephalitis virus and Powassan virus were examined using biophysical and computational modeling methods. First, we used size exclusion chromatography and analytical ultracentrifuge methods to investigate the purity of in-vitro transcribed RNAs. Next, we employed small-angle X-ray scattering techniques to study solution conformation and low-resolution structures of these RNAs, which suggest that the 3' terminal regions are highly extended as compared to the 5' terminal regions for both viruses. Using computational modeling tools, we reconstructed 3-dimensional structures of each RNA fragment and compared them with derived small-angle X-ray scattering low-resolution structures. This approach allowed us to reinforce that the 5' terminal regions adopt more dynamic structures compared to the mainly double-stranded structures of the 3' terminal regions.

show abstract

Section: Discussionmentioning

confidence: 99%

Nanoscale Structure Determination of Murray Valley Encephalitis and Powassan Virus Non-Coding RNAs

Mrozowich

Henrickson

Demeler

et al. 2020

Viruses

View full text Add to dashboard Cite

show abstract

“…Also, the highly expressed HMGA2 could increase the drug resistance of pancreatic cancer to chemotherapeutic drugs, as exhibited by Dangi-Garimella et al [37]. Due to its characteristics, HMGA2 is regarded as an oncogene, and HMGA2 protein AT-hook2 has two phosphorylation sites, serine at which can be phosphorylated by cyclin/CDKs at the beginning of S phase and during G 2 /M phase of the cell cycle, so it can influence cell differentiation and proliferation [38,39]. More importantly, HMGA2 can promote the malignant transformation of ovarian cancer cells, advance cancer cell invasion, and metastasis, and facilitate the growth and proliferation of ovarian cancer cells [40].…”

Section: Discussionmentioning

confidence: 99%

LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis

et al. 2019

View full text Add to dashboard Cite

This paper tried to explore ANRIL expression in ovarian cancer and how it affects cisplatin-sensitivity of ovarian cancer cells via regulation of let-7a/high-mobility group protein A2 (HMGA2) axis. qRT-PCR was used to detect ANRIL and let-7a levels in ovarian cancer tissues and cell lines (SKOV3 and SKOV3/DDP). Then cells were randomly assigned into Blank, negative control siRNA, ANRIL siRNA, let-7a inhibitor, and ANRIL siRNA+let-7a-inhibitor groups. CCK-8 assay was applied for assessing cell viability of cells treated with different concentrations of cisplatin. Flow cytometry was employed to test cell apoptosis rate. qRT-PCR and Western blot were performed for related molecules detection. Nude mice transplanted with SKOV3/DDP cells were used to confirm the effects of ANRIL siRNA on the cisplatin-sensitivity. Ovarian cancer tissues and cisplatin-resistant cells had increased ANRIL expression and decreased let-7a expression, and those patients with higher clinical stage and pathological grade showed higher ANRIL and lower let-7a. Dual-luciferase reporter-gene assay confirmed the targeting relationship between ANRIL and let-7a, and between let-7a and HMGA2. The cell viability and cisplatin IC50 were decreased in ANRIL siRNA group exposed to different concentrations of cisplatin, with enhanced apoptosis, as well as elevated let-7a and declined HMGA2, which would be reversed by let-7a inhibitor. Meanwhile, ANRIL down-regulation enhanced the inhibitory effect of cisplatin on tumor growth of nude mice and reduced tumor weight. Silencing ANRIL expression reduced HMGA2 expression to promote the apoptosis and improve cisplatin-sensitivity of ovarian cancer cells via up-regulating let-7a expression.

show abstract

“…Most studies point to an oncogenic role for HMGA2. In cancer and embryonic stem cells, HMGA2 bound to and stabilized replication forks (RFs), thereby promoting cell proliferation [ 12 ]. Xie et al illustrated that HMGA2 was of great importance to cadmium (Cd)-involved reactive oxygen species (ROS) production and proliferation in MRC-5 cells.…”

Section: Introductionmentioning

confidence: 99%

Emerging roles for HMGA2 in colorectal cancer

Wang

2021

Translational Oncology

View full text Add to dashboard Cite

HMGA2 (High Mobility Group AT-hook 2) has been reported to promote colorectal cancer (CRC) development by regulating the transcription of target genes. It participates in nearly all aspects of cellular processes, including cell transformation, proliferation, apoptosis, senescence, metastasis, epithelial-to-mesenchymal transition (EMT), DNA repair and stem cell self-renewal. In the past decades, a group of downstream targets and binding partners have been identified in a wide range of cancers. Our findings of HMGA2 as a key factor in the MDM2/p53, IL11/STAT3 and Wnt/β-catenin signaling pathways prompt us to summarize current advances in the functional and molecular basis of HMGA2 in CRC. In this review, we address the roles of HMGA2 in the oncogenic networks of CRC based on recent advances. We review its aberrant expression, explore underlying mechanisms, discuss its pro-tumorigenic effects, and highlight promising small-molecule inhibitors based on targeting HMGA2 here. However, the understanding of HMGA2 in CRC progression is still elusive, thus we also discuss the future perspectives in this review. Collectively, this review provides novel insights into the oncogenic properties of HMGA2, which has potential implications in the diagnosis and treatment of CRC.

show abstract

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

Cited by 17 publications

References 69 publications

Nanoscale Structure Determination of Murray Valley Encephalitis and Powassan Virus Non-Coding RNAs

Nanoscale Structure Determination of Murray Valley Encephalitis and Powassan Virus Non-Coding RNAs

LncRNA ANRIL affects the sensitivity of ovarian cancer to cisplatin via regulation of let-7a/HMGA2 axis

Emerging roles for HMGA2 in colorectal cancer

Contact Info

Product

Resources

About