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

整合 RNA 测序和单细胞质谱流式细胞术揭示 LncRNA HOXA-AS2 在肝细胞癌的肿瘤发生和干细胞中的新作用

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作者:Qinchen Lu #, Jiamin Gao #, Shaomei Tang #, Zhijian Li, Xi Wang, Caiwang Deng, Jiaxin Hu, Yuting Tao, Qiuyan Wang

Conclusion

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.

Methods

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

Purpose

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). Materials and

Results

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.

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