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Series GSE71342 Query DataSets for GSE71342
Status Public on Mar 31, 2016
Title RNA binding protein TIA1 cytoplasmic expression as an Independent Prognostic Factor in Human Esophageal Squamous Cell Carcinoma (ESCC).
Organism Homo sapiens
Experiment type Other
Summary T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein modulating many regulatory aspects of target mRNA metabolism. Despite several reports referring to the role of TIA1 in carcinogenesis, little is known about the significance of its expression and function in human cancers including esophageal squamous cell carcinoma (ESCC). In the present study, we found that ectopic localization of overexpressed TIA1 in the cytoplasm was observed in a cohort of 143 ESCC patients using immunohistochemistry, and the cytoplasmic TIA1 was an independent prognosticator for worse overall survival. Moreover, we revealed that TIA1 was overexpression in many ESCC cell lines, and silencing of TIA1 in those cells inhibited cell growth with an accumulation of cells in G0–G1 and sub-G1 phases. The human TIA1 gene generates two major protein isoforms, TIA1a and TIA1b. Expression of TIA1a isoform tended to be higher than that of TIA1b in ESCC cells, and TIA1a was expressed both in the nucleus and cytoplasm but TIA1b was expressed mainly in the nucleus. Further studies revealed that each isoform showed opposite effects on cell proliferation through ectopically introducing each gene: TIA1a promotes anchorage-dependent and independent cell proliferation, whereas TIA1b inhibits cell proliferation and/or induces cell death. The ribonucleoprotein immunoprecipitation followed by a microarray analysis or massive-parallel sequencing identified a set of TIA1-associating mRNAs including enriched cell cycle-associated genes. Among them, SKP2 and CCNA2 mRNA were shown to be interacted with TIA1 protein through their different regions, and SKP2 and CCNA2 protein levels were positively regulated by TIA1 through suppression of mRNA decay and translational induction, respectively. These findings provide new insights into the previously unknown role of TIA1 and its isoforms as tumor-promoting molecules regulating a set of downstream oncogenic proteins, and implicate their potential application as a useful marker of malignant potential and a therapeutic target in ESCC.
Overall design To investigate the target molecules regulated by TIA1 in esophageal squamous cell carcinoma cell line (KYSE180), the expression levels of mRNAs (total) and transcripts captured by RIP with TIA1 antibody (TIA1_RIP) were analyzed using microarray.
Contributor(s) Hamada J, Shoda K, Masuda K, Naruto T, Fujita Y, Komoto T, Miyagami Y, Kudoh Y, Ichikawa D, Otsuji E, Imoto I
Citation(s) 26958940
Submission date Jul 24, 2015
Last update date Jan 09, 2018
Contact name Kiyoshi Masuda
Organization name Institute of Biomedical Sciences, Tokushima University Graduate School
Department Department of Human Genetics
Street address 3-18-15 Kuramoto-cho
City Tokushima
ZIP/Postal code 770-8503
Country Japan
Platforms (1)
GPL17077 Agilent-039494 SurePrint G3 Human GE v2 8x60K Microarray 039381 (Probe Name version)
Samples (4)
GSM1832794 KYSE180_TIA1_RIP_1
GSM1832795 KYSE180_TIA1_RIP_2
GSM1832796 KYSE180_total_1
BioProject PRJNA290929

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE71342_RAW.tar 12.2 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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