Translated Long Non-Coding Ribonucleic Acid ZFAS1 Promotes Cancer Cell Migration by Elevating Reactive Oxygen Species Production in Hepatocellular Carcinoma

Autor: Xue-Xi Yang, Xiang-Ming Zhai, Yu Meng, Chen Xie, Min Li, Tian-Cai Liu, Ying-Song Wu, Zhi-Wei Guo, Kun Li, Chun-Lian Zhou, Na Zhao
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Frontiers in Genetics, Vol 10 (2019)
Frontiers in Genetics
ISSN: 1664-8021
Popis: Micropeptides (≤100 amino acids) are essential regulators of physiological and pathological processes, which can be encoded by small open reading frames (smORFs) derived from long non-coding RNAs (lncRNAs). Recently, lncRNA-encoded micropeptides have been shown to have essential roles in tumorigenesis. Since translated smORF identification remains technically challenging, little is known of their pathological functions in cancer. Therefore, we created classifiers to identify translated smORFs derived from lncRNAs based on ribosome-protected fragment sequencing and machine learning methods. In total, 537 putative translated smORFs were identified and the coding potential of five smORFs was experimentally validated via green fluorescent protein-tagged protein generation and mass spectrometry. After analyzing 11 lncRNA expression profiles of seven cancer types, we identified one validated translated lncRNA, ZFAS1, which was significantly up-regulated in hepatocellular carcinoma (HCC). Functional studies revealed that ZFAS1 can promote cancer cell migration by elevating intracellular reactive oxygen species production by inhibiting nicotinamide adenine dinucleotide dehydrogenase expression, indicating that translated ZFAS1 may be an essential oncogene in the progression of HCC. In this study, we systematically identified translated smORFs derived from lncRNAs and explored their potential pathological functions in cancer to improve our comprehensive understanding of the building blocks of living systems.
Databáze: OpenAIRE