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  • br In this study we demonstrated the

    2022-09-17


    In this study, we demonstrated the correlation between lncRNAs and adjacent genes using the expression of HEATR6 and lncRNA, LOC105371849, which were tightly correlated in breast cancer cell lines. Knockdown of lncRNA LOC105371849 decreased the level of HEATR6 mRNA expression which resulted in some changes in cell
    siRNA1 siRNA2 siRNA3
    Expression level to GAPDH 
    Non treat
    ns
    ns
    Control siRNA
    siRNA2
    Non treat Control siRNA siRNA2 Non treat Control siRNA siRNA2
    Non treat Ctrl siRNA siRNA 2 ER PR HER2
    positive
    Bax
    ExpressionleveltoGAPDH 1.5 ns
    Non treat Control siRNA siRNA2
    1.5 *** Expressionlevel
    toGAPDH 1.0
    Non treat Control siRNA siRNA2 
    Expressionlevel toGAPDH 1.0
    negative
    Non treat Control siRNA siRNA2
    Expressionlevel toGAPDH **
    Grade
    Non treat Control siRNA siRNA2
    Fig. 5. Putative roles of HEATR6 in breast cancer A) Morphology of HEATR6 knockdown MCF7 cell with control cells. Scale = 100 μm. B) Relative gene expressions of cell apoptosis and proliferation markers. *, **, *** and **** indicates p-value < .05, 0.01, 0.001 and 0.0001. ns means not significant. C) KM-plot analysis using affymatrix probes (218991_at) for HEATR6. Survival data was depicted in three different molecular subtypes (ER, PR, HER2) and grades. Black: low expression, red: high expression. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
    morphology. Since some cytotoxicity was found in cancer cell lines with a knockdown of lncRNA LOC105371849, we analyzed the level of BAX and BCL2 gene expression but no significant changes were found. However, the expression of proliferation markers (MKI67 and CCND1)
    was decreased in cancer Dexmedetomidine transfected with siLOC105371849lncRNA. This result suggests that lncRNA LOC105371849 may be involved in cell proliferation in breast cancer via HEATR6 regulation. Furthermore, KM plotter analysis revealed that high expression level of HEATR6 in certain molecular subtype and cancer grade II and III is associated with low survival rate of breast cancer patients.
    5. Conclusions
    This study screened lncRNAs functionally linked to breast cancer and tested their potential role in the regulation of neighboring BCAGs. This might be an efficient way increase understanding of the regulation mechanisms of various genes in associated diseases. Using this proce-dure, we indeed demonstrated the association of HEATR6 and its ad-jacent lncRNA (LOC105371849), and putative HEATR6 functions in breast cancer proliferation in certain molecular subtypes and stages. It might be important for a better understanding of breast cancer biology and could potentially be a predictor for the prognosis of breast cancer in patients.
    Acknowledgements
    The authors would like to thank Prof. Han-Byul Lee at the College of Medicine, Seoul National University, for kindly providing the breast cancer cell lines. 
    Funding statement
    This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT & Future Planning (2016M3A9B6026771) and partially by (#2016R1A6A3A11932951).
    References
    Amaral, P.P., et al., 2011. lncRNAdb: a reference database for long noncoding RNAs.
    Gonzalez, I., et al., 2015. A lncRNA regulates alternative splicing via establishment of a splicing-specific chromatin signature. Nat. Struct. Mol. Biol. 22, 370–376.
    Van Poznak, C., et al., 2015. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American society of clinical oncology clinical practice guideline. J. Oncol. Pract. 11, 514–516.