Differential expression of alternatively spliced transcripts related to energy metabolism in colorectal cancer.

Anastasiya V Snezhkina ,Alex Zhavoronkov,Anastasiya Isaevna Afremova,Irina Yurievna Karpova,Anastasiya V Lipatova ,K M Nyushko ,A Yu Popov ,Д В Кочетков ,Maria S Fedorova ,George S Krasnov ,D V Kalinin ,Nataliya V Melnikova ,Alexey A Dmitriev ,Andrew R Zaretsky ,Boris Alekseev ,А Д Каприн ,Alexey Moskalev ,А Ф Садритдинова ,Д В Сидоров ,Н Н Волченко ,Anna V Kudryavtseva

doi:10.1186/s12864-016-3351-5

Abstract

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. In the present work, we have studied the alterations of alternative splicing patterns of genes related to energy metabolism in CRC.ResultsUsing CrossHub software, we analyzed The Cancer Genome Atlas (TCGA) RNA-Seq datasets derived from colon tumor and matched normal tissues. The expression of 1014 alternative mRNA isoforms involved in cell energy metabolism was examined. We found 7 genes with differentially expressed alternative transcripts whereas overall expression of these genes was not significantly altered in CRC. A set of 8 differentially expressed transcripts of interest has been validated by qPCR. These eight isoforms encoded by OGDH, COL6A3, ICAM1, PHPT1, PPP2R5D, SLC29A1, and TRIB3 genes were up-regulated in colorectal tumors, and this is in concordance with the bioinformatics data. The alternative transcript NM_057167 of COL6A3 was also strongly up-regulated in breast, lung, prostate, and kidney tumors. Alternative transcript of SLC29A1 (NM_001078177) was up-regulated only in CRC samples, but not in the other tested tumor types.ConclusionsWe identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC. Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3351-5) contains supplementary material, which is available to authorized users.

Highlights

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide
We identified tumor-specific expression of alternative spliced transcripts of seven genes involved in energy metabolism in CRC
Our results bring new knowledge on alternative splicing in colorectal cancer and suggest a set of mRNA isoforms that could be used for cancer diagnosis and development of treatment methods

Summary

Introduction

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide. CRC molecular pathogenesis is heterogeneous and may be followed by mutations in oncogenes and tumor suppressor genes, chromosomal and microsatellite instability, alternative splicing alterations, hypermethylation of CpG islands, oxidative stress, impairment of different signaling pathways and energy metabolism. Colorectal cancer (CRC) is the third most common cancer in the world [1]. It accounts for more than 1,360,000 new cancer incidences and about 9% of all cancer deaths worldwide [2], [http://gco.iarc.fr/]. 20% of patients with CRC have already developed metastatic disease at the time of diagnosis [6, 7]. Identification of new therapeutic targets and biomarkers is imperative for the development of CRC therapies and diagnosis

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