Hsa_Circ_0098181 Suppresses Hepatocellular Carcinoma by Sponging miR-18a-3p and Targeting PPARA

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, and its incidence is still high in China. This study aimed to investigate the circular RNAs (circRNAs) involved in the development of HCC and elucidate the mechanism. RNA sequencing found 72 downregulated circRNAs and 88 upregulated circRNAs in human HCC tissues, including hsa_circ_0098181, hsa_circ_0072309, hsa_circ_0000831, and hsa_circ_0000231. The reduction of hsa_circ_0098181 was confirmed in eight paired human HCC tissues, hepatoma cell lines, and CCL4/DEN-induced mouse HCC models by RT-qPCR. The FISH assay revealed that hsa_circ_0098181 is mainly located in the cytoplasm of hepatocytes in the paratumor tissues. Further log-rank analysis performed in 91 HCC patients demonstrated that low expression of hsa_circ_0098181 was related to poor prognosis. The plasmid and lentivirus overexpressing hsa_circ_0098181 were delivered into HCC cell lines. After hsa_circ_0098181 was upregulated, the proliferation, invasion, migration, and colony formation of HCC cell lines were inhibited, and the apoptosis was promoted. Moreover, exogenous hsa_circ_0098181 delivery mitigated the tumor formation ability of Huh7 in Balb/C nude mice. The dual-luciferase reporter assay and the RIP assay verified that hsa_circ_0098181 sponged miR-18a-3p to regulate PPARA. In addition, a rescue experiment found miR-18a-3p mimic partly reversed the suppression of hsa_circ_0098181 on proliferation, invasion, and migration of HCC cell lines. In conclusion, hsa_circ_0098181 can repress the development of HCC through sponging miR-18a-3p and promoting the expression of PPARA in vitro and in vivo, and hsa_circ_0098181 might be a therapeutic target for HCC.

Wnt/β-catenin-driven EMT regulation in human cancers

“…Increasing evidence reveals that circRNAs may modulate EMT in cancers [ 209 ]. More importantly, circRNAs can decrease miRNA expression via sponging [ 210 ]. The overall aim of current section is to evaluate role of circRNAs in EMT regulation via targeting Wnt.…”

Recent research progress of circular RNAs in hepatocellular carcinoma

“…As the primary modulator of lipid metabolism, Peroxisome proliferator-activated receptor-α (PPARA) was deemed to be a promising HCC treatment. Hsa_circ_0098181 engaged in the miR-18a-3p/PPARA signaling pathway to exert anti-HCC effects ( 27 ). By physically attaching to CAPRIN1 and G3BP1, circVAMP3 exhibited tumor suppressor qualities in HCC by causing CAPRIN1 to phase separate and promoting the production of stress granules, which prevented the translation of c-Myc ( 28 ).…”

Illuminating Shared Genetic Associations Between Oesophageal Carcinoma and Pulmonary Carcinoma Risk

“…These sets encompassed pathways such as breast cancer 5p15 amplicon, DNA metabolic process, reactome highly calcium permeable postsynaptic nicotinic acetylcholine receptors, EHMT2 targets up, reactome highly calcium permeable nicotinic acetylcholine receptors, regulation of xenophagy, PPARA pathway, PTEN pathway, RNA binding and genomic pathway. Previous literature has provided substantial evidence linking these significantly enriched pathways to cancer initiation and progression, as observed in bladder cancer [38], gastric cancer [39], cervical cancer [40], lung cancer [41][42][43], and others associated with the amplification or alteration of 5p15; the close association between the PPARA pathway and various cancers [44][45][46]; as well as the role of the PTEN pathway in tumorigenesis [47][48][49]. Tissue-specific MAGMA analysis indicated that the spleen exhibited the highest enrichment evidence for both diseases, suggesting a strong immune correlation (Fig.…”