Abstracts Category : Other

Identify Metastasis-related LncRNA in Breast Cancer by Microarray Approach

by Ya-Ting Tu

Breast cancer occurs in mammary gland epithelial tissue and is the most commonly diagnosed cancer in women throughout the world. Previous studies indicated that invasion of cancer cells was the major cause of the death, which had been a major challenge in the treatment of breast cancer. In human genome, recent studies reveal that there is < 2 % of the total genome sequence as protein-coding genes, however, at least 98 % of genome are transcribed into non-coding RNA (ncRNA). So far, the study of ncRNA is mainly concentrated on the microRNA (miRNA) and long non-coding RNA (lncRNA). An increasing number of researches reveal that ncRNAs have been shown to play an important role in gene regulation, normal cellular functions and disease processes. However, the detail biological function of lncRNA involving in breast metastasis is still unclear. In this study, we performed the expression profiles of two breast cancer cell lines, MB-231-P and MB-231-IV2-1, by microarray approach (Agilent SurePrint G3 Human V2 GE; including 34092 protein-coding genes and 8715 lncRNAs). After finishing the microarray profiling, we identified about 213 lncRNAs upregulated and 301 lncRNAs downregulated in MB-231-IV2-1 cell line compared to MB-231-P, respectively. Finally, we successfully identified several metastasis-related lncRNA candidates according microarray data and The Cancer Genome Atlas (TCGA). Among them, LINC01420 was selected for further study in this study. We assessed the expression levels of LINC01420 in breast cancer tissues by real-time PCR approach. Our data revealed that the expression levels of LINC01420 were significantly increased in breast cancer compared with adjacent normal tissues. We further identified the full length of LINC01420 by 5 and 3 rapid amplification of cDNA ends (RACE) in breast cancer cell. Our results revealed that LINC01420 could generate three splicing transcripts (V1, V2 and V3) via alternative splicing. Furthermore, knockdown of LINC01420 could suppress breast cancer cell growth by inducing cell cycle arrest at S phase. Interesting, the cell growth and the invasion ability of MB-231-IV2-1 cell significantly decreased after LINC01420-V1 and -V3 knockdown. These results implied that LINC01420-V1 and -V3 might be critical isoforms and exon 2 might be a functional oncogene region involving in modulating biological function in breast cancer. Our results suggest that LINC01420 might be a functional oncogene in breast tumorigenesis.Advisors/Committee Members: Kuo-Wang Tsai (committee member), Sung-Chou Li (chair), Huey-Wen Shyu (chair), Ming-Hong Tai (committee member).