Research Paper Volume 13, Issue 21 pp 24037—24049
MiRNA-30e downregulation increases cancer cell proliferation, invasion and tumor growth through targeting RPS6KB1
- 1 BGI College and Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
- 2 Academy of Medical Science, Zhengzhou University, Zhengzhou, China
- 3 Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
- 4 Department of Medical Oncology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Received: June 3, 2021 Accepted: October 25, 2021 Published: November 2, 2021https://doi.org/10.18632/aging.203665
How to Cite
Copyright: © 2021 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Human esophagus carcinoma (EC) is one of the most common malignant tumors, especially in Africa and Asia including China. In EC initiation and progression, genetic and epigenetic aberrations have been reported to play a major role, but the underlying molecular mechanisms are largely unknown. In this study, the miR-30e levels were analyzed in human EC tissues and TCGA databases, and the results demonstrated that miR-30e expression in EC tissues was significantly decreased compared to adjacent normal tissues. To further investigate the role of miR-30e in cancer cells, we found that forced expression of miR-30e dramatically inhibited cell proliferation, invasion, tube formation, and colony formation of cancer cells. To determine the underlying mechanism of miR-30e, we found that RPS6KB1 was a direct target of miR-30e by binding to its 3′-UTR, which was verified by luciferase activity assay using reporters with wild-type miR-30e and its seed sequence mutant constructs and Western blotting assay. In vivo experiment showed that miR-30e overexpression significantly inhibited tumor growth and decreased RPS6KB1 expression in xenografts. In EC, high expression of RPS6KB1 in tumor tissues indicated poor prognosis of patients with less survival rate. High levels of RPS6KB1 and low levels of miR-30e closely correlated poor survival of patients with several other types of cancer. These findings show that miR-30e and its target RPS6KB1 are important in cancer development and clinical outcomes, and miR-30e/RPS6KB1 is a potential future therapeutic pathway for EC intervention.