Long Non-coding RNA TMEM220-AS1 Suppressed Hepatocellular Carcinoma by Regulating the miR-484/MAGI1 Axis as a Competing Endogenous RNA

Abstract

Long non-coding RNAs (lncRNAs) have a considerable regulatory influence on multiple biological processes. Nevertheless, the role of TMEM220-AS1 in hepatocellular carcinoma (HCC) remains unclear. We used The Cancer Genome Atlas (TCGA) database to analyze the differentially expressed lncRNAs. qRT-PCR was used to verify the results for a large population. The in vitro effects of TMEM220-AS1 on HCC cells were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), flow cytometry, and Transwell assays in HCC cells. We used qRT-PCR and western blotting to identify the epithelial-mesenchymal transition (EMT). Moreover, we performed bioinformatics analysis, western blotting, dual luciferase reporter gene assay, RNA pull-down, and RNA binding protein immunoprecipitation (RIP) to investigate the underlying molecular mechanisms of TMEM220-AS1 function. Finally, the function of TMEM220-AS1 was verified in vivo. The results showed that TMEM220-AS1 was expressed at considerably low levels in HCC. It was demonstrated that malignant phenotypes and EMT of HCC cells were promoted by the knock down of TMEM220-AS1 both in vivo and in vitro. TMEM220-AS1, which was detected primarily in the cytoplasm, functioned as an miRNA sponge to bind miR-484 and promote the level of membrane-associated guanylate kinase, WW, and PDZ domain containing 1 (MAGI1), thereby curbing the malignant phenotypes of HCC cells. In conclusion, low levels of TMEM220-AS1 promote proliferation and metastasis through the miR-484/MAGI1 axis in HCC.

miR-484: A Potential Biomarker in Health and Disease

“…The physiological functions of miR-484 in mammals are multifaceted and involve endoplasmic reticulum stress, oxidative stress, inflammation, cell proliferation and apoptosis. Besides, several reports have confirmed the abnormal expression of miR-484 in both tissue and serum specimens from clinical patients (29,30,32). The modalities and regulatory mechanisms of miR-484 regulation of downstream target genes in different types of cells and their microenvironments are unique.…”

“…Consistency with the former, hypermethylation at the CpG island site of the miR-484 promoter in microsatellite instability colorectal cancer significantly downregulates miR-484 production ( 33 ). In apart from the above mechanisms, mature miRNAs compete with long-stranded non-coding RNAs (lncRNAs) to bind the 3’-UTR of target mRNAs and indirectly inhibit the negative regulation of target genes by miRNAs, such as lncRNA Ttc3-209 in human retinal cells ( 24 ), PGM5-AS1 in colorectal cancer ( 28 ), TMEM220-AS1 in hepatocellular carcinoma cells ( 29 ), THAP9-AS1 in pancreatic ductal adenocarcinoma ( 30 ) and PCED1B-AS1 in Clear Cell Renal Cell Carcinoma ( 27 ), which are considered as ceRNAs, by competitively inhibiting miR-484 binding and upregulating the translation of target proteins.…”

Pyroptosis-Related LncRNA Signature Predicts Prognosis and Is Associated With Immune Infiltration in Hepatocellular Carcinoma

“…The pathogenesis of HCC is very complicated, involving transcriptional misregulation and cell cycle disorder ( 26 , 27 ), somatic mutation ( 27 ) and abnormal pyroptosis ( 28 ). LncRNAs can affect tumorigenesis and tumor progression in a variety of ways, including regulation of cell proliferation and apoptosis ( 29 ), influencing drug sensitivity ( 30 ), and regulation of cell pyroptosis ( 31 ). Various prognostic prediction models for HCC patients based on lncRNA signatures have been reported ( 22 , 32 , 33 ).…”

The Pyroptosis-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Immunotherapeutic Efficiency in Hepatocellular Carcinoma

“…Numerous studies have suggested that lncRNAs play a key role in the occurrence, development, and metastasis of liver cancer, and they have shown strong survival prediction potential as novel biomarkers ( Hong et al, 2020 ; Li et al, 2020 ; Wan et al, 2021 ; Zhou et al, 2021 ). For example, Cao reported that lncRNA TMEM220-AS1 could suppress HCC cell proliferation and metastasis by regulating the miR-484/MAGI1 axis ( Cao et al, 2021 ). However, the prognostic value and mechanism of pyroptosis-related lncRNAs in HCC have not yet been elucidated and remain to be studied.…”