Comprehensive circular RNA profiling identifies CircFAM120A as a new biomarker of hypoxic lung adenocarcinoma

Xinghua Cheng, Jin Qiu, Sainan Wang, Yunhai Yang, Mingwei Guo, Dongmei Wang, Qingquan Luo, Lingyan Xu


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.