Long non-coding RNA ILF3-AS1 facilitates hepatocellular carcinoma progression by stabilizing ILF3 mRNA in an m6A-dependent manner.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Increasing evidences have demonstrated that ILF3 antisense RNA 1 (ILF3-AS1) acts as an oncogenic long noncoding RNA (lncRNA) in several types of human cancers. However, the expression pattern, functional role and underlying mechanism of ILF3-AS1 in HCC remains largely unclear. Here, we found that ILF3-AS1 expression was significantly elevated in HCC tissues and also associated with prognosis of patients with HCC. Functional assays demonstrated that knockdown of ILF3-AS1 expression resulted in the suppression of proliferation, migration and invasion in HCC cells, whereas overexpression of ILF3-AS1 exerted opposite effects. Additionally, knockdown of IFL3-AS1 attenuated HCC tumorigenesis and metastasis in vivo. Mechanistically, ILF3-AS1 associated with ILF3 mRNA and inhibited its degradation. ILF3-AS1 increased ILF3 m6A level via recruiting N6-methyladenosine (m6A) RNA methyltransferase METTL3. Moreover, IFL3-AS1 enhanced the interaction between ILF3 mRNA and m6A reader IGF2BP1. Overall, our study revealed the function and mechanism of ILF3-AS1 in the malignant phenotypes of HCC cells, which provides a novel therapeutic target for HCC.