Abstract
BackgroundAbundant evidence has manifested that long noncoding RNAs (lncRNAs) are closely implicated in human cancers, including hepatocellular carcinoma (HCC). Remarkably, lncRNA FAM83H antisense RNA 1 (FAM83H-AS1) has been reported to be a tumor-propeller in multiple cancers. However, its effect on HCC progression remains unknown.MethodsFAM83H-AS1 expression was analyzed by RT-qPCR. Colony formation, EdU, and flow cytometry as well as transwell assays were implemented to analyze the biological functions of FAM83H-AS1 on HCC progression. Luciferase reporter, RIP and RNA pull-down assays were implemented to detect the interaction among FAM83H-AS1, microRNA-485-5p (miR-485-5p), and myocyte enhancer factor 2D (MEF2D) in HCC cells.ResultsFAM83H-AS1 expression in HCC cells was markedly elevated. FAM83H-AS1 accelerated cell proliferation, migration and invasion whereas inhibiting cell apoptosis in HCC. Besides, we confirmed that FAM83H-AS1 acts as a miR-485-5p sponge in HCC cells. Additionally, MEF2D was verified to be a direct target of miR-485-5p. FAM83H-AS1 could upregulate MEF2D expression via sponging miR-485-5p. Further, rescue experiments testified that MEF2D upregulation or miR-485-5p downregulation offset the repressive effect of FAM83H-AS1 depletion on HCC cell progression.ConclusionsFAM83H-AS1 facilitates HCC malignant progression via targeting miR-485-5p/MEF2D axis, suggesting that FAM83H-AS1 may be a promising biomarker for HCC treatment in the future.
Highlights
Abundant evidence has manifested that long noncoding RNAs are closely implicated in human cancers, including hepatocellular carcinoma (HCC)
FAM83H-AS1 is expressed at high levels in HCC cell lines and promotes HCC cell progression Recent studies have revealed an obvious elevation of FAM83H-AS1 expression in multiple cancers, including bladder cancer and glioma [16, 17], yet the level of FAM83H-AS1 in HCC remains unknown
Cell apoptosis was observably enhanced after the depletion of FAM83H-AS1 (Fig. S1C, Fig. 1E)
Summary
Abundant evidence has manifested that long noncoding RNAs (lncRNAs) are closely implicated in human cancers, including hepatocellular carcinoma (HCC). LncRNA FAM83H antisense RNA 1 (FAM83HAS1) has been reported to be a tumor-propeller in multiple cancers. A penetrated investigation on the underlying molecular mechanism of HCC progression is still the priority for identifying potential biomarkers to develop effective strategies for HCC treatment. LncRNAs are crucial meditators of tumorigenesis by exerting biological functions and inducing regulatory mechanisms in multiple human cancers [12]. Among the regulatory mechanisms, competing endogenous RNA (ceRNA) network is the most prevalent in regulating cellular behaviors of diverse malignancies, including HCC. HIF1A-AS2 propels the progression of colorectal cancer via the regulatory axis of miR-129-5p/DNMT3A [13]. We further investigated the other regulatory mechanism of FAM83HAS1 in HCC in terms of ceRNA network
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