NDLI: Analysis of an independent tumor suppressor locus telomeric to Tp53 suggested Inpp5k and Myo1c as novel tumor suppressor gene candidates in this region

Content Provider	Springer Nature : BioMed Central
Author	Hedberg Oldfors, Carola Dios, Diego Garcia Linder, Anna Visuttijai, Kittichate Samuelson, Emma Karlsson, Sandra Nilsson, Staffan Behboudi, Afrouz
Abstract	Background Several reports indicate a commonly deleted chromosomal region independent from, and distal to the TP53 locus in a variety of human tumors. In a previous study, we reported a similar finding in a rat tumor model for endometrial carcinoma (EC) and through developing a deletion map, narrowed the candidate region to 700 kb, harboring 19 genes. In the present work real-time qPCR analysis, Western blot, semi-quantitative qPCR, sequencing, promoter methylation analysis, and epigenetic gene expression restoration analyses (5-aza-2´-deoxycytidine and/or trichostatin A treatments) were used to analyze the 19 genes located within the candidate region in a panel of experimental tumors compared to control samples. Results Real-time qPCR analysis suggested Hic1 (hypermethylated in cancer 1), Inpp5k (inositol polyphosphate-5-phosphatase K; a.k.a. Skip, skeletal muscle and kidney enriched inositol phosphatase) and Myo1c (myosin 1c) as the best targets for the observed deletions. No mutation in coding sequences of these genes was detected, hence the observed low expression levels suggest a haploinsufficient mode of function for these potential tumor suppressor genes. Both Inpp5k and Myo1c were down regulated at mRNA and/or protein levels, which could be rescued in gene expression restoration assays. This could not be shown for Hic1. Conclusion Innp5k and Myo1c were identified as the best targets for the deletions in the region. INPP5K and MYO1C are located adjacent to each other within the reported independent region of tumor suppressor activity located at chromosome arm 17p distal to TP53 in human tumors. There is no earlier report on the potential tumor suppressor activity of INPP5K and MYO1C, however, overlapping roles in phosphoinositide (PI) 3-kinase/Akt signaling, known to be vital for the cell growth and survival, are reported for both. Moreover, there are reports on tumor suppressor activity of other members of the gene families that INPP5K and MYO1C belong to. Functional significance of these two candidate tumor suppressor genes in cancerogenesis pathways remains to be investigated.
Related Links	https://bmcgenomdata.biomedcentral.com/counter/pdf/10.1186/s12863-015-0238-4.pdf
Ending Page	13
Page Count	13
Starting Page	1
File Format	HTM / HTML
ISSN	27306844
DOI	10.1186/s12863-015-0238-4
Journal	BMC Genomic Data
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2015-07-14
Access Restriction	Open
Subject Keyword	Life Sciences Animal Genetics and Genomics Microbial Genetics and Genomics Plant Genetics and Genomics Genetics and Population Dynamics Tp53 Hic1 Inpp5k Skip Myo1c Endometrial carcinoma 17p13.3 RNO10q24-q25
Content Type	Text
Resource Type	Article
Subject	Health Informatics Genetics
Journal Impact Factor	1.9/2023
5-Year Journal Impact Factor	1.9/2023

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Analysis of an independent tumor suppressor locus telomeric to Tp53 suggested Inpp5k and Myo1c as novel tumor suppressor gene candidates in this region

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