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Malek, J. A.

Publications and source records attributed to Malek, J. A..

2 recordsLinked to original sources

Silencing of ANKRD12 circRNA induces molecular and functional changes associated with invasive phenotypes

Circular RNAs (circRNA) that form through non-canonical backsplicing events of pre-mRNA transcripts are evolutionarily conserved and abundantly expressed across species. However, the functional relevance of circRNAs remains a topic of debate. 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. The circANKRD12 is RNase R resistant and predominantly localized in the cytoplasm in contrast to its source gene mRNA. We confirmed the expression of this circRNA across a variety of cancer cell lines and provide evidence for its functional relevance through downstream regulation of several tumor invasion genes. 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.

cancer biology

Genus-wide sequencing supports a two-locus model for sex-determination in Phoenix

The date palm tree is a commercially important member of the genus Phoenix whose 14 species are all dioecious with separate male and female individuals. Previous studies identified a multi-megabase region of the date palm genome linked to sex and showed that dioecy likely developed in Phoenix prior to speciation. To identify genes critical to sex determination we sequenced the genomes of 28 Phoenix trees representing all 14 species. Male-specific sequences were identified and extended using phased single molecule sequencing or BAC clones to distinguish X and Y alleles.\n\nHere we show that only four genes contain sequences conserved in all analyzed males, likely identifying the changes foundational to dioecy in Phoenix. The majority of these sequences show similarity to a single genomic locus in the closely related oil palm. CYP703 and GPAT3, two genes critical to male flower development in other monocots, appear fully deleted in females while maintained as single copy in males. A LOG-like gene appears translocated into the Y chromosome and a cytidine deaminase-like appears at the border of a chromosomal rearrangement. Our data supports a two-mutation model for the evolution from hermaphroditism to dioecy through a gynodioecious intermediate.

genomics