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Cancer Res Treat. 2019 Jan;51(1):391-401. doi: 10.4143/crt.2018.103. Epub 2018 Jun 14.

NFATC3-PLA2G15 Fusion Transcript Identified by RNA Sequencing Promotes Tumor Invasion and Proliferation in Colorectal Cancer Cell Lines.

Author information

1
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
2
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University College of Medicine, Seoul, Korea.
3
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
4
Department of Chemistry, College of Science, Yonsei University, Seoul, Korea.

Abstract

PURPOSE:

This study was designed to identify novel fusion transcripts (FTs) and their functional significance in colorectal cancer (CRC) lines.

Materials and Methods:

We performed paired-end RNA sequencing of 28 CRC cell lines. FT candidates were identified using TopHat-fusion, ChimeraScan, and FusionMap tools and further experimental validation was conducted through reverse transcription-polymerase chain reaction and Sanger sequencing. FT was depleted in human CRC line and the effects on cell proliferation, cell migration, and cell invasion were analyzed.

RESULTS:

One thousand three hundred eighty FT candidates were detected through bioinformatics filtering. We selected six candidate FTs, including four inter-chromosomal and two intrachromosomal FTs and each FT was found in at least one of the 28 cell lines. Moreover, when we tested 19 pairs of CRC tumor and adjacent normal tissue samples, NFATC3-PLA2G15 FT was found in two. Knockdown of NFATC3-PLA2G15 using siRNA reduced mRNA expression of epithelial-mesenchymal transition (EMT) markers such as vimentin, twist, and fibronectin and increased mesenchymal-epithelial transition markers of E-cadherin, claudin-1, and FOXC2 in colo-320 cell line harboring NFATC3-PLA2G15 FT. The NFATC3-PLA2G15 knockdown also inhibited invasion, colony formation capacity, and cell proliferation.

CONCLUSION:

These results suggest that that NFATC3-PLA2G15 FTs may contribute to tumor progression by enhancing invasion by EMT and proliferation.

KEYWORDS:

Colorectal neoplasms; Fusion transcript; NFATC3; PLA2G15; RNA-sequencing

PMID:
29909608
PMCID:
PMC6333966
DOI:
10.4143/crt.2018.103
[Indexed for MEDLINE]
Free PMC Article

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