HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells DOI Creative Commons
Xi Yang,

Ziyang Luo,

Qingfang Zheng

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 19, 2023

Abstract Pancreatic cancer is one of the most malignant tumor types characterized by high metastasis ability and low survival rate. As a chromatin-binding protein, HMGA2 widely overexpressed considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that highly expressed in pancreatic tissues promotes malignancy through cell proliferation, metastasis, xenograft growth vivo. Moreover, enhanced cellular redox status inhibiting reactive oxygen species promoting glutathione. Importantly, significantly ameliorated ferroptotic death was observed cells overexpressing HMGA2. Conversely, deletion exacerbated ferroptosis. Mechanistically, activated GPX4 expression regulation at transcription translation levels. promoted cis-element modification promoter region gene enhancing enhancer activity increased H3K4 methylation H3K27 acetylation. Furthermore, stimulated protein synthesis via mTORC1-4EBP1 -S6K signaling axis. The overexpression alleviated decreased level resulting from pharmacologic inhibition mTORC1. more pronouncedly reduced phosphorylation 4EBP1 S6K compared to control. A strong positive correlation between confirmed using immunohistochemistry staining. We also mitigated sensitivity combination treatment ferroptosis inducer mTORC1 or gemcitabine. In summary, our results revealed mechanism which coordinates underscores potential value targeting treatment.

Language: Английский

From LncRNA to metastasis: The MALAT1-EMT axis in cancer progression DOI
Riya Thapa, Obaid Afzal, Muhammad Afzal

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 253, P. 154959 - 154959

Published: Nov. 19, 2023

Language: Английский

Citations

50
Targeting RNA splicing modulation: new perspectives for anticancer strategy? DOI Creative Commons
Xuemei Lv, Xiaoyu Sun, Yang Gao

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 30, 2025

Language: Английский

Citations

2
Comprehensive review for non-coding RNAs: From mechanisms to therapeutic applications DOI
Yanjun Zhang,

Lijuan Zhan,

Xue Jiang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 224, P. 116218 - 116218

Published: April 21, 2024

Language: Английский

Citations

15
HMGA2 alleviates ferroptosis by promoting GPX4 expression in pancreatic cancer cells DOI Creative Commons
Ziyang Luo, Qingfang Zheng, Shazhou Ye

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 16, 2024

Abstract Pancreatic cancer is one of the most malignant tumor types and characterized by high metastasis ability a low survival rate. As chromatin-binding protein, HMGA2 widely overexpressed considered an oncogene with various undefined regulatory mechanisms. Herein, we demonstrated that highly expressed in pancreatic tissues, mainly distributed epithelial cells, represents subtype epithelial–mesenchymal transition. Deletion inhibits malignancy through cell proliferation, metastasis, xenograft growth vivo. Moreover, enhanced cellular redox status inhibiting reactive oxygen species promoting glutathione production. Importantly, ferroptotic death was significantly ameliorated cells overexpressing HMGA2. Conversely, deletion exacerbated ferroptosis. Mechanistically, activated GPX4 expression transcriptional translational regulation. binds promotes cis-element modification promoter region gene enhancing enhancer activity increased H3K4 methylation H3K27 acetylation. Furthermore, stimulated protein synthesis via mTORC1-4EBP1 -S6K signaling axes. The overexpression alleviated decrease levels resulting from pharmacologic inhibition mTORC1. compared control, more strongly reduced phosphorylation 4EBP1 S6K. A strong positive correlation between confirmed using immunohistochemical staining. We also mitigated sensitivity to combination treatment ferroptosis inducer mTORC1 or gemcitabine. In summary, our results revealed mechanism which coordinates underscores potential value targeting treatment.

Language: Английский

Citations

8
MicroRNAs: a symphony orchestrating evolution and disease dynamics DOI Creative Commons
Shan Quah, Gowtham Subramanian, Jonathan S.L. Tan

et al.

Trends in Molecular Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Language: Английский

Citations

8
HMGA2 promotes cancer metastasis by regulating epithelial–mesenchymal transition DOI Creative Commons
Qing Ma, Sisi Ye,

Hong Liu

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Feb. 1, 2024

Epithelial–mesenchymal transition (EMT) is a complex physiological process that transforms polarized epithelial cells into moving mesenchymal cells. Dysfunction of EMT promotes the invasion and metastasis cancer. The architectural transcription factor high mobility group AT-hook 2 (HMGA2) highly overexpressed in various types cancer (e.g., colorectal cancer, liver breast uterine leiomyomas) significantly correlated with poor survival rates. Evidence indicated HMGA2 overexpression markedly decreased expression marker E-cadherin (CDH1) increased vimentin (VIM), Snail, N-cadherin (CDH2), zinc finger E-box binding homeobox 1 (ZEB1) by targeting transforming growth beta/SMAD (TGFβ/SMAD), mitogen-activated protein kinase (MAPK), WNT/beta-catenin (WNT/β-catenin) signaling pathways. Furthermore, new class non-coding RNAs (miRNAs, circular RNAs, long RNAs) plays an essential role HMGA2-induced accelerating process. In this review, we discuss alterations highlight promoting tumor growth, migration, invasion. More importantly, extensively mechanism through which regulates most cancers, including pathways interacting RNA axis. Thus, elucidation molecular mechanisms underlie effects on patient mediating may offer therapeutic methods for preventing progression.

Language: Английский

Citations

6
DNA Nanoframework-Confined Well-Organized Catalytic Hairpin Assembly for Highly Sensitive and Specific Detection of MiRNA DOI

Yongbin Hou,

Yong Huang,

Yan-e Du

et al.

Talanta, Journal Year: 2025, Volume and Issue: 290, P. 127788 - 127788

Published: Feb. 21, 2025

Language: Английский

Citations

0
A novel mechanism in regulating drug sensitivity, growth, and apoptosis of bortezomib-resistant multiple myeloma cells: the USP4/KLF2/HMGA2 cascade DOI Creative Commons
Ziyi Liu, Xiaoliang Li,

Y. He

et al.

Journal of Orthopaedic Surgery and Research, Journal Year: 2025, Volume and Issue: 20(1)

Published: March 1, 2025

Multiple myeloma (MM) is a malignant disorder originating from plasma cells. Bortezomib (BTZ) resistance has become huge obstacle to MM treatment. Herein, we elucidated the action of Kruppel-like factor 2 (KLF2), crucial transcription (TF), on BTZ MM. Two BTZ-resistant cell lines (MM1.S/BTZ and NCI-H929/BTZ) were generated used. KLF2 mRNA was quantified by quantitative PCR, protein expression analyzed immunoblotting. MTT cytotoxicity assay used test sensitivity. Cell growth detected EdU assays. Flow cytometry for apoptosis cycle distribution analyses. The USP4/KLF2 relationship examined Co-IP stability KLF2/HMGA2 interplay confirmed luciferase ChIP Upregulation observed in serum Depletion suppressed enhanced sensitivity MM1.S/BTZ NCI-H929/BTZ Moreover, USP4 increased deubiquitination affected growth, via KLF2. functioned as regulator HMGA2 modulated through HMGA2. Additionally, two lines. Our study demonstrates role USP4/KLF2/HMGA2 cascade regulating cells, providing novel targets improving anti-MM efficacy BTZ.

Language: Английский

Citations

0
Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer DOI Creative Commons

Weiyu Su,

Weiwen Wang, Guanghui Zhang

et al.

Clinical Epigenetics, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 13, 2025

Signal transduction plays a pivotal role in modulating myriad of critical processes, including the tumour microenvironment (TME), cell cycle arrest, proliferation and apoptosis cells, as well their migration, invasion, epithelial–mesenchymal transition (EMT). Epigenetic mechanisms are instrumental genesis progression tumours. The Chromobox (CBX) family proteins, which serve significant epigenetic regulators, exhibit tumour-specific expression patterns biological functionalities. These proteins influenced by multitude factors could modulate activation diverse signalling pathways within cells through alterations modifications, thereby acting either oncogenic agents or suppressors. This review aims to succinctly delineate composition, structure, function, CBXs with an emphasis on synthesizing deliberating CBXs-mediated intracellular intricate governing tumourigenesis progression. Moreover, plethora contemporary studies have substantiated that might represent promising target for diagnosis therapeutic intervention patients. We also compiled scrutinized current research landscape concerning inhibitors targeting CBXs, aspiring aid researchers gaining deeper comprehension roles malignant evolution tumours, furnish novel perspectives innovation targeted therapeutics.

Language: Английский

Citations

0
HMGA2 overexpression activates IGF2BP2 to stabilize APLP2 via m6A modification and promote pancreatic cancer progression DOI Creative Commons
Ke Liu,

Congbing Wei,

Haixin Yu

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e27268 - e27268

Published: Feb. 28, 2024

Pancreatic cancer is a highly aggressive malignancy of the digestive system, with occult onset, rapid progression, and poor prognosis. The genetic heterogeneity pancreatic contributes to its malignant biological behavior. HMGA2 overexpressed in tumors known regulate tumor progression various cancers through HMGA2-IGF2BP2 axis, but role mechanism remain unclear. In this study, we demonstrated that promotes progression. We further revealed upregulates IGF2BP2, which stabilizes APLP2 mRNA via m6A modification, thereby promoting These results indicate HMGA2/IGF2BP2/APLP2 signaling axis regulates cancer.

Language: Английский

Citations

3