MYC-Induced Upregulation of Lncrna ELFN1-AS1 Contributes to Tumor Growth in Colorectal Cancer via Epigenetically Silencing TPM1

Abstract

Abstract Recently, long noncoding RNAs (lncRNA) have been reported as tumor suppressors or oncogenes in colorectal cancer. This study aims to discover functional role of a novel lncRNA in colorectal cancer tumorigenesis. Expression profile of fibronectin type III domain containing 1 antisense RNA 1 (ELFN1-AS1) in colorectal cancer samples was displayed on TCGA database. Expression level of ELFN1-AS1 was tested in colorectal cancer tissues and cell lines via qRT-PCR. Functional role of ELFN1-AS1 was assessed by loss-of-function assays. Mechanism experiments, such as chromatin immunoprecipitation (ChIP) assay and luciferase reporter assay, were done to analyze the molecular mechanism of ELFN1-AS1 in colorectal cancer. ELFN1-AS1 knockdown inhibited colorectal cancer tumor growth through restricting cell proliferation and facilitating cell apoptosis. ELFN1-AS1 was transcriptionally activated by MYC. Moreover, ELFN1-AS1 led to transcriptional silencing of tropomyosin 1 (TPM1) via recruiting enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and forkhead box P1 (FOXP1). Collectively, MYC-upregulated ELFN1-AS1 recruited EZH2 and FOXP1 to restrain TPM1 expression, thereby promoting colorectal cancer tumor growth. Implications: This study revealed a novel molecular pathway in colorectal cancer progression, which may provide new method for early diagnosis and treatment of colorectal cancer.