Loss of ATP5A1 Enhances Proliferation and Predicts Poor Prognosis of Colon Adenocarcinoma

Abstract Background ATP Synthase F1 Subunit Alpha (ATP5F1A), also named as ATP5A1, is a subunit of mitochondrial ATP synthase. Dysregulated expression of ATP5A1 has been reported in several malignancies, nevertheless it showed either oncogenic or tumor-suppressing roles in different cancer types. Here we aimed to initially investigate the expression and role of ATP5A1 in colon adenocarcinoma. Methods We firstly evaluated the transcription and mRNA levels of ATP5A1 using data from The Cancer Genome Atlas (TCGA). Besides, we tested its mRNA and protein expression in our enrolled retrospective cohort (n=115). Univariate and multivariate analyses were conducted to assess its prognostic value. Cellular experiments and xenografts in mice model were performed to validate the role of ATP5A1 in colon cancer. Results ATP5A1 showed a significant lower level in colon adenocarcinoma than in adjacent nontumorous tissue. Advanced tumor stage was characterized with lower ATP5A1 level. Lower ATP5A1 was associated with poor prognosis in both TCGA dataset (P=0.041) and our cohort (P=0.001). Furthermore, Cox regression analysis demonstrated that ATP5A1 was a novel independent prognostic factor for colon cancer patients (HR=0.43, P=0.018). Finally, cellular and xenografts data confirmed that overexpressing ATP5A1 can remarkably attenuate colon cancer growth. Conclusion Low expression of ATP5A1 may be a potential molecular marker for poor prognosis in colon cancer. Data availability Data will be available upon request.