Discipline: Biological Sciences
Subcategory: Cancer Research
Room: Virginia A
Bayan Bokhari - Howard University
Co-Author(s): Swetha Parvathaneni, Howard University, Washington, DC; Xing Lu, Howard University Washington, DC; and Sudha Sharma Howard University, Washington, DC
RECQ1, also known as RECQL or RECQL1, is a DNA helicase that plays an essential role in maintaining genomic stability. Our lab has demonstrated that in addition to its role in DNA repair, RECQ1 also modulates gene expression in breast cancer cells. Recent studies show that inactivating mutations in RECQ1 increase susceptibility to develop breast cancer. However, the molecular role of RECQ1 in breast tumorigenesis is yet unknown. We hypothesize that RECQ1 regulates the expression of specific genes and pathways critical for tumorigenesis. To investigate RECQ1-regulated transcriptome, we performed RNA-Sequencing from CRISPR/Cas9-derived isogenic pair of RECQ1-wildtype and RECQ1-knockout MDA-MB-231 breast cancer cells. Using an arbitrary cut-off of 2-fold change in gene expression and adjusted p<0.05, we performed bioinformatic analysis for functional profiling of genes and pathways up- and downregulated by RECQ1. Then, we have validated RECQ1-target genes by real-time quantitative PCR and Western Blotting, as well as by performing genetic rescue experiments. Our transcriptomic data shows that RECQ1 significantly affects genes important for cell migration, invasion and proliferation. These results are complemented by functional assays using in vitro cell culture as well as xenograft studies done in mice in vivo. In conclusion, these results significantly advance our understanding of the molecular role of RECQ1 in breast cancer tumorigenesis. The Mechanistic understanding of gene regulation by RECQ1 in breast cancer development and progression is important to develop in future better strategies for the diagnosis and treatment of breast cancer patient.
Funder Acknowledgement(s): Bayan Bokhari is supported by Umm Al-Qura University, Saudi Arabia, Graduate Student Scholarship; this research work was supported by a grants Grant No. NSF1832163, NIGMS/NIH 5SC1GM093999, and NIA/NIH 1R25 AG047843 awarded to Sudha Sharma PhD, Department of Biochemistry and Molecular Biology; National Human Genome Center, College of Medicine, Howard University, Washington, DC, United States.
Faculty Advisor: Sudha Sharma, firstname.lastname@example.org
Role: My part was analyzing the RNA-seq and interpretation of the data using bioinformatic tools.