MYC-induced upregulation of lncRNA ELFN1-AS1 contributes to tumor growth in colorectal cancer via epigenetically silencing TPM1.

Recently, long noncoding RNAs (lncRNAs) have been reported as tumor suppressors or oncogenes in colorectal cancer (CRC). This study aims to discover functional role of a novel lncRNA in CRC tumorigenesis. Expression profile of fibronectin type III domain containing 1 antisense RNA 1 (ELFN1-AS1) in CRC samples was displayed on TCGA database. Expression level of ELFN1-AS1 was tested in CRC tissues and cell lines via quantitative real-time polymerase chain reaction (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 CRC. ELFN1-AS1 knockdown inhibited CRC 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 CRC tumor growth. Implications: This study revealed a novel molecular pathway in CRC progression, which may provide new method for early diagnosis and treatment of CRC.