LINC00205, a YY1-modulated lncRNA, serves as a sponge for miR-26a-5p facilitating the proliferation of hepatocellular carcinoma cells by elevating CDK6

T. Cheng, Y. Yao, S. Zhang, X.-N. Zhang, A.-H. Zhang, W. Yang, C.-Z. Hou

Department of General Surgery, Xi’an Children’s Hospital, Xi’an, China. chongzhihou@126.com

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• Oncology

OBJECTIVE: LINC00205, a bidirectional lncRNA, located at human chromosome 21q22.3, was recently characterized as an oncogenic molecule contributing to cell proliferation in several cancers, including hepatocellular carcinoma (HCC). In the present study, we aim to probe the new molecular mechanism for LINC00205 controlling the proliferation of HCC cells.

PATIENTS AND METHODS: The expression status of LINC00205, miR-26a-5p, as well as CDK6 in HCC tissues/cell lines was determined by quantitative real-time PCR (qPCR). The cell proliferative activity was measured by using the Cell Counting Kit (CCK)-8 assay. Flow cytometry was performed to analyze cell cycle progression and apoptosis induction. The interaction among LINC00205, miR-26a-5p and CDK6, as well as transcription efficiency of LINC00205 promoter were examined by Dual-Luciferase reporter assay. Western blot was conducted to evaluate the protein levels of CDK6 in SNU-449 cells. The direct interplay between YY1 and LINC00205 promoter was detected by ChIP-qPCR.

RESULTS: LINC00205 was strongly expressed in HCC tissues and cell lines. Elevated LINC00205 expression was positively associated with worse prognosis as well as pathological grade in HCC. Suppression of LINC00205 could impede the proliferation of HCC cells by triggering the G0/G1-phase cell cycle arrest and apoptosis in vitro. Mechanistically, we illustrated that LINC00205 could accelerate the proliferation of HCC cells by boosting CDK6 expression via sponging miR-26a-5p. Moreover, we unveiled that LINC00205 could be activated by transcription factor Yin Yang-1 (YY1) as its direct downstream target.

CONCLUSIONS: LINC00205, a novel YY1-modulated lncRNA, can facilitate the proliferation of HCC cells through YY1/miR-26a-5p/CDK6 pathway, and may serve as a promising diagnostic biomarker and therapeutic target for HCC.

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