Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
EIF1AX Promotes Cell Proliferation in Breast Cancer by Transcriptional Repression of P21
26 Pages Posted: 8 Apr 2019
More...Abstract
Background: Dysregulation of cell cycle has been implicated in the progression of malignant cancer, but the precise functional contributions are uncertain. Here, we report that EIF1AX promotes the proliferation of breast cancer cells by facilitating their G1/S transition through downregulation of p21 and consequently plays an important role in the development and progression of breast cancer.
Methods: The expression of EIF1AX in tissues from patients with breast cancer was analyzed via IHC and qRT-PCR. The effects of EIF1AX on cellular proliferation and tumorigenesis in breast cancer cells were determined. The correlation between EIF1AX expression and p21 expression was assessed. The mechanisms as to how EIF1AX regulates p21 in breast cancer were addressed.
Findings: EIF1AX promotes the proliferation of breast cancer cells by facilitating the G1/S cell-cycle transition. Mechanistic investigation revealed that EIF1AX acts at the transcriptional level to inhibit the expression of the critical cell-cycle regulator, p21. We further identified the transcriptional regulation of p21 by EIF1AX was p53-independent. Clinically, we found that levels of EIF1AX were significantly upregulated in breast cancer tissues, and EIF1AX expression levels correlated with worse survival rates for patients with breast cancer.
Interpretation: These results enhance our understanding of the oncogenic potential of EIF1AX, which will be useful for future studies on the prognosis and therapy of breast cancer.
Funding: This work was supported by the National Natural Science Foundation of China (31621004) and CAS Strategic Priority Research Program Grants (XDA16030403 to W.L.).
Declaration of Interest: The authors declare that no conflicts of interest exist.
Ethical Approval: The Ethics Committee of the Institute of Zoology approved this study and all patients gave their informed consent prior to surgery.
Keywords: EIF1AX, Cell proliferation, Breast cancer, p21
Suggested Citation: Suggested Citation