Integrated RNA Sequencing and Single-Cell Mass Cytometry Reveal a Novel Role of LncRNA HOXA-AS2 in Tumorigenesis and Stemness of Hepatocellular Carcinoma

Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in the development of many cancer types. However, the changes of lncRNAs expression profiles in hepatocarcinogenesis remain largely unknown. Therefore, the purpose of this study was to identify the clinical signi...

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Published in:OncoTargets and therapy 2020, Vol.13, p.10901-10916
Main Authors: Lu, Qinchen, Gao, Jiamin, Tang, Shaomei, Li, Zhijian, Wang, Xi, Deng, Caiwang, Hu, Jiaxin, Tao, Yuting, Wang, Qiuyan
Format: Article
Language:English
Subjects:
c-Myc protein
Cell growth
Cytometry
Experiments
Gene expression
Genetic transformation
Hepatocellular carcinoma
Laboratory animals
Liver cancer
Medical research
Metastasis
Myc protein
Non-coding RNA
Original Research
p53 Protein
Polymerase chain reaction
Proteins
Ribonucleic acid
RNA
Stem cell transplantation
Stem cells
Telomerase reverse transcriptase
Tumorigenesis
Wound healing
Xenografts
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Summary:Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play critical roles in the development of many cancer types. However, the changes of lncRNAs expression profiles in hepatocarcinogenesis remain largely unknown. Therefore, the purpose of this study was to identify the clinical significance, oncogenic functions, and potential mechanism of cancer-related lncRNAs in hepatocellular carcinoma (HCC). An in vitro hepatocellular carcinoma model was established via oncogene-mediated transformation with a combination of three genetic alterations, including hTERT overexpression, inactivation of P53, and KRAS activation. Changes of biological function and transcriptome profile in these cell lines were determined by colony formation assay, MTT assay, wound-healing scratch assay, xenograft nude mice model, mass cytometry and RNA sequencing (RNA-Seq). Furthermore, 116 HCC tissues and its corresponding normal tumor-adjacent tissues were explored to validate the results of cell lines. Finally, RNA sequencing, single-cell mass cytometry and fluorescence-activated cell sorter were applied to evaluate the potential association between the expression of lncRNA and the stemness of HCC. LncRNA HOXA-AS2 was aberrantly upregulated and it may be involved in the regulation of cancer stem cells during oncogenic transformation. Consistently, lncRNA HOXA-AS2 expression was significantly upregulated in HCC and its higher expression positively correlated with poor prognosis and stem cell-related functions. Moreover, a specific cancer stem cell subpopulation with EPCAM , C-MYC and CK19 may exist in higher HOXA-AS2 expression HCC patients. LncRNA HOXA-AS2 plays pivotal roles in the occurrence and progression of HCC, which may act as a therapeutic target for prognostic biomarker in hepatocellular carcinoma.
ISSN:1178-6930
1178-6930
DOI:10.2147/ott.S272717