circANKRD12 a potential cancer bio-marker controls cancer invasion and migration in breast and ovarian cancer cells


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Thasni Kardeath1, Ikhlak Ahmed1, Wafaa Al Ameri1, Fatima Al-Dasim1, Joel Malek1

1weill cornell medicine- qatar

Abstract

Background

Circular RNAs (circRNA) that form through non-canonical backsplicing events of pre-mRNA transcripts are evolutionarily conserved, highly stable and abundantly expressed across species. However, the functional relevance of circRNAs remains elusive. These qualities mark them to be a potential cancer biomarker or a specific therapeutic target.

Method

 

Breast and Ovarian cancer cells Cancer cell lines, MDA-MB-231 and SKOV3 cells were used for the study. Silencing of circAKRD12 and its linear RNA was done using RNAi method and validated by using Real Time PCR method. Over expression of circular ANKRD12 was done using circular mini vector PCDNA3.1 Gene expression analysis was done using RNA-Seq analysis using illumina HiSeq 4000 system. Functional and phenotypic analysis were done by cell proliferation assays, cell cycle analysis and 3D organotypic cells generation on circANKRD12 silenced cells.

Results

In this study, we identified and characterized a circular RNA derived from Exon 2 and Exon 8 of the ANKRD12 gene, termed here as circANKRD12. We show that this circRNA is abundantly expressed in breast and ovarian cancers with two isofoms. The circANKRD12 is RNase R resistant and predominantly localized in the cytoplasm in contrast to its source gene mRNA. We show that silencing of circANKRD12 induces a phenotypic change by significantly regulating cell cycle, increasing invasion and migration, altering the metabolism in cancer cells. These results reveal the functional significance of circANKRD12 and provide evidence of a regulatory role for this circRNA in cancer progression. Knockdown of  circANKRD12 affects several cell signaling pathways including cell cycle progression and immune modulatory pathways. We show that silencing and overexpressing of circANKRD12 induces a functionally relevant phenotypic changes.

Conclusion

       Iou.

These results reveal the functional significance of circANKRD12 and provide evidence of a regulatory role for this circRNA in cancer progression and can be a potential biomarker for either cancer diagnosis or prognosis.