Long Non-coding RNA AC009686.2 Promotes Breast Cancer Cells Proliferation and Invasion / 中国生物化学与分子生物学报

ABSTRACT

Long non-coding RNAs (LncRNAs) , as regulators of a class of gene expression, play a key role in the development of various types of tumor.We analyzed the TCGA database and found that the expression of LncRNA AC009686.2 in breast cancer tissues was significantly higher than that in normal tissues, and was positively correlated with the poor prognosis of breast cancer patients.qRT-PCR analysis showed that the expression of LncRNA AC009686.2 in breast cancer cells was significantly up-regulated, and the expression level of LncRNA AC009686.2 in MCF7, T47D, ZR7530, BT549, HCC1937, MDA- MB-231 and SKBR3 eells was 6.58, 5.66, 7.29, 9.06, 6.89, 11.17 and 5.38 folds of that in MCF10 A eells, respectively.LncRNA AC009686.2 knockdown in MDA-MB-231 and BT549 cells which expressed relatively high LncRNA AC009686.2 significantly inhibited cell proliferation, colony formation and invasion, and induced cell G,/S phase arrest.The clone inhibition rates of MDA-MB-231 and BT549 cells with LncRNA AC009686.2 knockdown were 0.496%, 0.438% and 0.495%, 0.353% of the control group, respectively.LncRNA AC009686.2 knockdown also down-regulated protein levels of cyclinD2 and ZEB1.However, overexpression of ZEB1 could significantly reverse the decrease of cell invasion ability caused by LncRNA AC009686.2 knockdown.We further analvsed in the software JASPAR database and found that LncRNA AC009686.2 promoter had ZEB1 binding site, and overexpression of ZEB1 could down-regulate the expression level of LncRNA AC009686.2 in breast cancer cells.In conclusion, LncRNA AC009686.2 which highly expressed in breast cancer, promotes cell proliferation and invasion by up-regulating cyclinD2 and ZEB1 expression, while ZEB1 positively regulates LncRNA AC009686.2 expression.This study will provide a theoretical basis for elucidating the role of LncRNA AC009686.2 in breast cancer and related molecular mechanisms.