Abstract 165: Common long noncoding RNAs (lncRNA) with altered expression levels in colorectal adenoma and carcinoma
Authors: Kalmar Alexandra , Nagy Zsofia B. , Galamb Orsolya , Wichmann Barnabas , Bartak Barbara K. , Tulassay Zsolt , Molnar Bela 
Published: August 2015

Background: Among several functions long non-coding RNAs (lncRNA) are known to act as crucial epigenetic regulators of cell proliferation. Their expression level alterations can lead to cancer formation. Identification of lncRNA expression profiles in colorectal adenoma and cancer (CRC) would be beneficial to expand our knowledge of CRC development.

Aims: This study aimed to identify differentially expressed long non-coding RNAs (lncRNA) in colorectal adenoma and CRC cases.

Materials and methods: Total RNA was isolated from 94 human colonic biopsy samples (27 CRCs, 29 colonic adenomas, 38 normal donors without evidence of disease) with Qiagen Mini Kit. Expression levels of lncRNAs were analyzed with HGU133Plus2.0 microarrays (Affymetrix). Affymetric probe sets of 2090 lncRNAs already represented on this array type were extracted with non-coding (“NR”) Refseq IDs. Furthermore, total RNA including miRNAs was isolated from 20 independent biopsy samples (7 CRCs, 6 colonic adenomas, 7 normal donors without evidence of disease) with High Pure miRNA Isolation Kit (Roche) and expression levels of 40.914 non-protein coding transcripts were analyzed by using Human Transcriptome Array 2.0 (Affymetrix). Data were analysed using Expression Console and Transcriptome Analysis Console softwares (Affymetrix).

Results: According to HGU133Plus2.0 microarray results 3 significantly upregulated lncRNAs were identified in adenomas and 4 in CRCs, while 10 significantly downregulated lncRNAs were found in adenomas and 12 in CRC compared to the healthy controls (p&lt;0.05; -1≥logFc≥1). On the basis of the Human Transcriptome array results -analyzing broader range of non-coding RNAs- 76 upregulated lncRNAs were detected in adenomas and 97 in CRC, while 51 downregulated lncRNAs were found in adenomas and 45 in CRC compared to the healthy controls (p&lt;0.05; -1≥logFc≥1). 100% of the lncRNAs showing significant gene expression alteration on HGU133Plus2.0 arrays showed similar expression alteration tendency on Human Transcriptome arrays in the adenoma vs. normal and 88% in the CRC vs. normal comparisons. Interestingly, 44% of lncRNAs upregulated in CRC samples showed significantly elevated expression (p&lt;0.05) already in adenoma samples (e.g. upregulated CRNDE, lincFAM75A7-18, linc-FAM135A, lincDUSP26-1 and downregulated linc-DCLK3-2, linc-AMN1, linc-SOD3-2, lincFAM55D compared to healthy controls) containing lncRNAs already associated with CRC or other types of cancer.

Conclusion: The identified lncRNAs with significantly altered expression levels sequence can play a central role in the regulation of transcription during colorectal adenoma-carcinoma. Common up- or downregulated lncRNAs in colorectal adenoma and in CRC samples can be the basis of further investigations in order to enhance early detection of the colorectal cancer development.

Citation Format: Alexandra Kalmar, Zsofia B. Nagy, Orsolya Galamb, Barnabas Wichmann, Barbara K. Bartak, Zsolt Tulassay, Bela Molnar. Common long noncoding RNAs (lncRNA) with altered expression levels in colorectal adenoma and carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 165. doi:10.1158/1538-7445.AM2015-165