The Role of RECQL4 Overexpression in Gene Regulation and Cancer Development: Implications of Effective Targeted Therapy
DOI:
https://doi.org/10.58445/rars.3017Keywords:
RECQL4, Cancer Prognosis, RT-qPCR, Western Blotting, Wound Healing Assay, Flow Cytometry, Drug ResistanceAbstract
The RECQL4 gene is located on human chromosome 8 and codes for a homonymous helicase. This gene plays a crucial role in DNA repair, replication, and recombination. Specifically, the coded enzyme participates in a wide variety of DNA repair pathways and preserves its structural integrity. However, such protective functions are often compromised by RECQL4 upregulation, which is potentially caused by mutation-induced gene amplification and deregulation. An overexpression of the RECQL4 gene leads to increases in cell proliferation and genomic instability and is highly correlated to cancer progression. Due to RECQL4 overexpression across multiple tumor types, the present study proposes that such a phenomenon has the ability to serve as a measure of cancer prognosis. To test this hypothesis, the level of RECQL4 expression across three types of cancer cell samples (HCC cells, breast and ovarian cancer cells) were measured via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and RECQL4 helicase abundance was assessed via western blotting. In addition, the RECQL4 genes within half of the cell samples were temporarily silenced, and the samples were analyzed via wound-healing assay to assess the effect of reduced RECQL4 activity on the cancer cells’ self-repair mechanisms and invasiveness. The cell cycle of RECQL4-inhibited cells were then compared with original samples via flow cytometry. Lastly, the risk scores and IC50 values of sorafenib, doxorubicin, and cisplatin are then evaluated to determine the impact of RECQL4 inhibition on responsiveness of cancer cells to current treatments. Overall, the study revealed an unusually high level of RECQL4 expression in all three types of cancer cells, showed a decrease in the invasiveness of cells with an inhibited RECQL4 gene, and discovered an unexpected relationship between RECQL4 overexpression and drug resistance.
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