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.
ABSTRACT
OBJECTIVE: Contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) is a valuable device to diagnose and determine the malignant potential of gastrointestinal stromal tumors (GIST) as early as possible when making clinical therapeutic decisions. This study aimed to estimate the ability of CH-EUS to discriminate between GIST and benign submucosal lesions (SML) and to predict their malignant potential. METHODS: PubMed, MEDLINE, EMBASE, the Web of Science, and Cochrane Central Register of Controlled Trials databases were screened. Using the data provided in the literatures, 2 × 2 tables were constructed to obtain the pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. A receiver operating characteristic (ROC) curve was generated and the area under the ROC curve (AUROC) was calculated. RESULTS: Four studies with a total of 187 patients were identified to evaluate the value of CH-EUS in discriminating between GIST and benign SML. The pooled sensitivity, specificity, and AUROC were 89% (95% CI 0.82-0.93), 82% (95% CI 0.66-0.92), and 0.89, respectively. Five studies including 143 patients were analyzed to assess the accuracy of CH-EUS in determining the malignant potential of GIST. The pooled sensitivity, specificity, and AUROC curve of CH-EUS were 96% (95% CI 0.90-0.99), 53% (95% CI 0.40-0.66), and 0.92, respectively. CONCLUSIONS: CH-EUS is a safe, noninvasive method that can distinguish between GIST and benign subepithelial lesions and to predict their malignant potential to a certain extent. Large-scale, multicenter prospective studies are needed in the future.