A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancer.

Journal Article

The homeobox A (HOXA) region of protein-coding genes impacts female reproductive system embryogenesis and ovarian carcinogenesis. The 5-prime end of HOXA includes three long non-coding RNAs (lncRNAs) (HOXA10-AS, HOXA11-AS, and HOTTIP) that are underexplored in epithelial ovarian cancer (EOC). We evaluated whether common genetic variants in these lncRNAs are associated with EOC risk and/or have functional roles in EOC development. Using genome-wide association study data from 1,201 serous EOC cases and 2,009 controls, an exonic variant within HOXA11-AS, rs17427875 (A>T), was marginally associated with reduced serous EOC risk (OR = 0.88 (95% CI: 0.78-1.01, p = 0.06). Functional studies of ectopic expression of HOXA11-AS minor allele T in EOC cells showed decreased survival, proliferation, migration, and invasion compared to common allele A expression. Additionally, stable expression of HOXA11-AS minor allele T reduced primary tumor growth in mouse xenograft models to a greater extent than common allele A. Furthermore, HOXA11-AS expression levels were significantly lower in human EOC tumors than normal ovarian tissues (p < 0.05), suggesting that HOXA11-AS has a tumor suppressor function in EOC which may be enhanced by the T allele. These findings demonstrate for the first time a role for HOXA11-AS in EOC with effects that could be modified by germline variants.

Full Text

Duke Authors

Cited Authors

  • Richards, EJ; Permuth-Wey, J; Li, Y; Chen, YA; Coppola, D; Reid, BM; Lin, H-Y; Teer, JK; Berchuck, A; Birrer, MJ; Lawrenson, K; Monteiro, ANA; Schildkraut, JM; Goode, EL; Gayther, SA; Sellers, TA; Cheng, JQ

Published Date

  • October 2015

Published In

Volume / Issue

  • 6 / 33

Start / End Page

  • 34745 - 34757

PubMed ID

  • 26430965

Electronic International Standard Serial Number (EISSN)

  • 1949-2553

International Standard Serial Number (ISSN)

  • 1949-2553

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.5784

Language

  • eng