LncRNA STEAP3-AS1 Modulates Cell Cycle Progression via Affecting CDKN1C Expression Through STEAP3 in Colon Cancer

Abstract

Background: Previous studies have reported that lncRNAs have acted as new players during tumorigenesis by gene regulation in the transcriptional and posttranscriptional levels. Metallothionein plays an important role in tumorigenesis and progression. It is mainly considered to be involved in the process of cell proliferation, oxidative stress and multidrug resistance. However, the potential involvement of metallothionein-related long noncoding RNAs (lncRNAs) in colon cancer remains poorly understood. Methods: Those MT1M-related lncRNAs were screened out by lncRNA microarray assay. Detection of lncRNA STEAP3-AS1 expression in colon cancer tissue and cell lines was conducted by qRT-PCR and bioinformatic analysis. MTT, transwell migration, wound-healing and cell-cycle assays were investigated for the biological properties of STEAP3-AS1 in vitro. Additionally, a xenograft model of human colon cancer was established for the tumor growth effect of STEAP3-AS1 in vivo. Furthermore, we disclosed its mechanism in colon cancer by qRT-PCR, Western blot, bioinformatics, etc. Findings: We found that MT1M affects the expression of lncRNA STEAP3-AS1. STEAP3-AS1, located in physical contiguity with STEAP3, was notably increased in colon cancer tissues and cells. In vitro assay, knockdown of STEAP3-AS1 could inhibit colon cancer cells proliferation, migration and arrest colon cancer cells at the G0-G1 phase. In tumorigenicity assay, STEAP3-AS1 knockdown could strongly inhibit tumor growth. Mechanistic investigations demonstrated that STEAP3-AS1 downregulation could increase the expression of cyclin dependent kinase inhibitor 1C (CDKN1C) by STEAP3 upregulation. Interpretation: Overall, we identify the underlying role of MT1M-related lncRNA STEAP3-AS1 in colon cancer progression, which provides a novel strategy for colon cancer therapy. Funding: This work was supported by grants from the Chinese National Science Foundation Projects (31470800, 81372669 and 31270867), the Science and Technology Planning Project of Liaoning province, China (2012225020), and the Project of Chinese Ministry of Health (W2012RQ23). Declaration of Interest: The authors declare that they have no competing interests. Ethical Approval: All animal experimental procedures were conducted by the Institutional Animal Care and Use Committee of Dalian Medical University.