Long-range interaction and correlation between MYC enhancer and oncogenic long noncoding RNA CARLo-5.

Proc Natl Acad Sci U S A

Department of Molecular Virology, Immunology and Medical Genetics and Department of Anesthesiology, Wexner Medical Center, and Department of Neurological Surgery, The Ohio State University, Columbus, OH 43210.

Published: March 2014

The mechanism by which the 8q24 MYC enhancer region, including cancer-associated variant rs6983267, increases cancer risk is unknown due to the lack of protein-coding genes at 8q24.21. Here we report the identification of long noncoding RNAs named cancer-associated region long noncoding RNAs (CARLos) in the 8q24 region. The expression of one of the long noncoding RNAs, CARLo-5, is significantly correlated with the rs6983267 allele associated with increased cancer susceptibility. We also found the MYC enhancer region physically interacts with the active regulatory region of the CARLo-5 promoter, suggesting long-range interaction of MYC enhancer with the CARLo-5 promoter regulates CARLo-5 expression. Finally, we demonstrate that CARLo-5 has a function in cell-cycle regulation and tumor development. Overall, our data provide a key of the mystery of the 8q24 gene desert.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964128PMC
http://dx.doi.org/10.1073/pnas.1400350111DOI Listing

Publication Analysis

Top Keywords

myc enhancer
16
long noncoding
16
noncoding rnas
12
long-range interaction
8
enhancer region
8
carlo-5 promoter
8
carlo-5
6
region
5
interaction correlation
4
myc
4

Similar Publications

Oncogenic role of RARG rearrangements in acute myeloid leukemia resembling acute promyelocytic leukemia.

Nat Commun

January 2025

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Acute myeloid leukemia (AML) featuring retinoic acid receptor-gamma (RARG) rearrangements exhibits morphological features resembling those of acute promyelocytic leukemia but is associated with drug resistance and poor clinical outcomes. However, the mechanisms underlying the role of RARG fusions in leukemogenesis remain elusive. Here, we show that RARG fusions disrupt myeloid differentiation and promote proliferation and self-renewal of hematopoietic stem and progenitor cells (HSPCs) by upregulating BCL2 and ATF3.

View Article and Find Full Text PDF

[Bioinformatics and animal experiments reveal mechanism of Linggui Zhugan Decoction in ameliorating chronic heart failure after myocardial infarction via HIF-1α/HO-1 signaling pathway].

Zhongguo Zhong Yao Za Zhi

December 2024

School of Integrated Chinese Medicine and Western Medicine, Anhui University of Chinese Medicine Hefei 230012, China Anhui Province Key Laboratory of Chinese Medicinal Formula Hefei 230012, China.

This study aims to investigate the effect of Linggui Zhugan Decoction(LGZGD) on autophagy in the mouse model of chronic heart failure(CHF) induced by myocardial infarction(MI), as well as the regulatory effect of LGZGD on the hypoxia-inducible factor-1α(HIF-1α)/heme oxygenase-1(HO-1) signaling pathway, based on bioinformatics and animal experiments. The active ingredients and corresponding targets of LGZGD were retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database, and GEO, GeneCards, and DisGeNET were searched for the disease targets. Cytoscape was used to establish a "drug-component-target" network.

View Article and Find Full Text PDF

The MCM6-c-Myc positive feedback loop mediates bladder cancer progression and cisplatin resistance.

Int J Biol Macromol

January 2025

Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urinary System Disease, Lanzhou, China. Electronic address:

Chemotherapy remains a cornerstone in the treatment of bladder cancer (BLCA); however, the development of chemoresistance substantially limits its efficacy and significantly affects patient survival. Thus, elucidating the molecular mechanisms underlying BLCA chemoresistance is critical to improving patient outcomes. Our study identified MCM6 as an oncogene that facilitates BLCA proliferation and invasion and is linked to cisplatin resistance.

View Article and Find Full Text PDF

Gene therapy in polycystic kidney disease: A promising future.

J Transl Int Med

December 2024

Division of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China.

Polycystic kidney disease (PKD) is a genetic disorder marked by numerous cysts in the kidneys, progressively impairing renal function. It is classified into autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD), with ADPKD being more common. Current treatments mainly focus on symptom relief and slowing disease progression, without offering a cure.

View Article and Find Full Text PDF

HDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAF-mutant microsatellite stable colorectal cancer.

J Immunother Cancer

January 2025

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, Beijing, China

Background: B-Raf proto-oncogene, serine/threonine kinase (BRAF)-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical attempts, such as BRAF inhibitors (BRAFi) monotherapy and combining BRAFi with other inhibitors, have yielded unsatisfactory efficacy. This study aims to identify a novel therapeutic strategy for this challenging subgroup.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!