Xinghua Cheng1, Jin Qiu2, Sainan Wang2, Yunhai Yang1, Mingwei Guo2, Dongmei Wang2, Qingquan Luo1, Lingyan Xu2. 1. Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China. 2. Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
Abstract
BACKGROUND: Hypoxia is crucial in the initiation and progression of tumor metastasis. Circular RNAs (CircRNAs) comprise a novel group of non-coding, RNase R resistant and regulatory RNAs which are generated by 'back-splicing' processes. However, the characterization and function of circRNAs in hypoxic cancer cells remain unknown. METHODS: High throughput RNA-seq assay was performed in lung adenocarcinoma cells (A549) under either normoxic or hypoxic conditions. Bioinformatic analysis of differentially expressed circRNAs was conducted and their target genes were predicted and partially confirmed. RESULTS: Hypoxia increased the expression of hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream genes in A549 cells and enhanced cell migration ability. Comprehensive analysis of global circRNAs expression profiles of A549 identified a total of 558 circRNAs candidates, among which 65 circRNAs were differentially expressed (35 upregulated and 30 downregulated) in hypoxic cancer cells. The difference in their circRNA expressions were compared by computational analysis and circRNA-miRNA networks were constructed. We further characterized one circRNA (hsa_circ_0008193) derived from the FAM120A gene and renamed it as circFAM120A. The expression of circFAM120A, as validated by reverse transcription polymerase chain reaction, was significantly downregulated in both hypoxic A549 and lung cancer tissue from patients with lymph node metastasis. Gene ontology (GO) enrichment analysis and KEGG pathway analysis revealed that circFAM120A may participate in lung cancer development. CONCLUSIONS: CircRNAs profiles were altered in lung adenocarcinoma under hypoxia and circFAM120A may have the potential to be a new biomarker of lung adenocarcinoma hypoxia. 2019 Annals of Translational Medicine. All rights reserved.
BACKGROUND: Hypoxia is crucial in the initiation and progression of tumor metastasis. Circular RNAs (CircRNAs) comprise a novel group of non-coding, RNase R resistant and regulatory RNAs which are generated by 'back-splicing' processes. However, the characterization and function of circRNAs in hypoxic cancer cells remain unknown. METHODS: High throughput RNA-seq assay was performed in lung adenocarcinoma cells (A549) under either normoxic or hypoxic conditions. Bioinformatic analysis of differentially expressed circRNAs was conducted and their target genes were predicted and partially confirmed. RESULTS: Hypoxia increased the expression of hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream genes in A549 cells and enhanced cell migration ability. Comprehensive analysis of global circRNAs expression profiles of A549 identified a total of 558 circRNAs candidates, among which 65 circRNAs were differentially expressed (35 upregulated and 30 downregulated) in hypoxic cancer cells. The difference in their circRNA expressions were compared by computational analysis and circRNA-miRNA networks were constructed. We further characterized one circRNA (hsa_circ_0008193) derived from the FAM120A gene and renamed it as circFAM120A. The expression of circFAM120A, as validated by reverse transcription polymerase chain reaction, was significantly downregulated in both hypoxic A549 and lung cancer tissue from patients with lymph node metastasis. Gene ontology (GO) enrichment analysis and KEGG pathway analysis revealed that circFAM120A may participate in lung cancer development. CONCLUSIONS: CircRNAs profiles were altered in lung adenocarcinoma under hypoxia and circFAM120A may have the potential to be a new biomarker of lung adenocarcinoma hypoxia. 2019 Annals of Translational Medicine. All rights reserved.
Authors: Roderick J Phillips; Javier Mestas; Mehrnaz Gharaee-Kermani; Marie D Burdick; Antonio Sica; John A Belperio; Michael P Keane; Robert M Strieter Journal: J Biol Chem Date: 2005-03-31 Impact factor: 5.157
Authors: Jes-Niels Boeckel; Nicolas Jaé; Andreas W Heumüller; Wei Chen; Reinier A Boon; Konstantinos Stellos; Andreas M Zeiher; David John; Shizuka Uchida; Stefanie Dimmeler Journal: Circ Res Date: 2015-09-16 Impact factor: 17.367