Breast-cancer anti-estrogen resistance 4 (BCAR4) encodes a novel maternal-effect protein in bovine and is expressed in the oocyte of humans and other non-rodent mammals

Abstract

This study provides a novel candidate gene whose mutation or deregulation may underlie certain cases of unexplained female infertility.

Investigating the role of BCAR4 in ovarian physiology and female fertility by genome editing in rabbit

“…These products are stored and are recruited following fertilisation to support the development of the transcriptionally quiescent early embryo; they are called maternal-effect genes (reviewed in reference 3 ). In our previous work, BCAR4-targeting siRNA affected bovine embryo development in vitro 9 , supporting the www.nature.com/scientificreports www.nature.com/scientificreports/ hypothesis that BCAR4 is a maternal-effect gene. Here, the delivery rate of homozygous +88/+88 females was very low (22 ± 7%), while the AI success rate of heterozygous +88/N females (71 ± 11%) was in the normal range.…”

“…Identification of the rabbit BCAR4 orthologue and ovarian expression. A rabbit BCAR4 orthologue was previously predicted 9 . Based on the rabbit OryCun2.0 genome sequence, it is located onto chromosome Ocu6, with the putative coding region between bases 5,255,378-5,255,713 on the minus strand.…”

“…An alternative, compensatory albeit suboptimal mechanism may have been activated in animals with a non-functional BCAR4 gene. As for the biological process underlying BCAR4 action, bovine embryo development rate was previously observed to be reduced when BCAR4-targeting siRNA were micro-injected into transcriptionally silent mature oocytes 9 , indicating that the effect is likely independent from transcription. It may rather result from post-transcriptional regulation of other maternal-effect transcripts or from stabilising or activating maternal-effect proteins.…”

“…Human BCAR4 was characterised in parallel as a marker of Tamoxifen resistant breast tumours, hence its name 7 , and has since been found to be expressed in various cancers 8 . BCAR4 transcripts are detected in fully grown oocytes in humans, cows, pigs, dogs and horses 9 . The bovine transcript follows a maternal profile: it decreases throughout embryo development and is not activated at the major embryonic gene activation.…”

Long Noncoding RNAs

“…Injection of BCAR4-expressing ZR-75-1 cells into nude mice resulted in rapidly growing tumors (Godinho et al 2011 ). Although BCAR4 is theoretically capable of encoding a protein (Angulo et al 2013 ;Meijer et al 2006 ), its noncoding function appears to be critical for breast cancer metastasis, acting as a downstream effector of chemokine CCL21 (Xing et al 2014 ). Although BCAR4 is theoretically capable of encoding a protein (Angulo et al 2013 ;Meijer et al 2006 ), its noncoding function appears to be critical for breast cancer metastasis, acting as a downstream effector of chemokine CCL21 (Xing et al 2014 ).…”