Abstract
Circular RNAs (circRNAs) have been recognized as significant participants in the progression of different cancers; however, the detailed mechanisms of circRNAs in hepatocellular carcinoma (HCC) remain unclear. In this study, hsa_circ_0001394 was identified by RNA-seq analysis, and hsa_circ_0001394 was determined to be highly expressed in HCC specimens and cell lines. Patients with high expression of hsa_circ_0001394 tended to exhibit poor survival. Increased hsa_circ_0001394 expression in plasma was closely correlated with clinicopathological features including elevated vascular invasion and an advanced TNM stage, as indicated by alpha-fetoprotein (AFP) analysis. Hsa_circ_0001394 promoted the proliferation, migration, and invasion of HCC cells, whereas knockdown of hsa_circ_0001394 inhibited HCC tumorigenesis in vivo. In addition, mechanistic studies showed that miR-527 negatively interacted with hsa_circ_0001394. Furthermore, UBE2A was revealed to serve as a target of miR-527. Overall, the present study suggested that hsa_circ_0001394 may function as a sponge to promote HCC progression by regulating the miR-527/UBE2A pathway. Thus, hsa_circ_0001394 may become a promising biomarker and potential therapeutic target in HCC treatment.
Highlights
Hepatocellular carcinoma (HCC) has emerged as a major contributor to the burden of cancer incidence globally and ranks third in cancer mortality, causing an estimated 0.83 million deaths per year [1]
Despite recent progress in HCC treatment, including immunotherapy and targeted therapy [2], the limited diagnostic methods that can be used at an early stage result in poor prognosis [3], thereby highlighting the importance of exploring HCC therapeutic targets and their detailed downstream mechanisms [4]
Another study indicated that circRNA-104718 enhances HCC progression by sponging the miR-218-5p tumor inhibitor by targeting TXNDC5 [32]
Summary
Hepatocellular carcinoma (HCC) has emerged as a major contributor to the burden of cancer incidence globally and ranks third in cancer mortality, causing an estimated 0.83 million deaths per year [1]. CircRNAs consist of mainly exons [9] or introns [10], and they generally exist in the cytoplasm, in contrast to their corresponding linear RNAs, due to their lack of polyadenylated (poly(A)) tails and 5′ caps [11]. Due to their ring loop structures, circRNAs are more stable than their linear counterparts [12]. Targeting miRNAs, which can serve as either tumor inhibitors or oncogenes by interacting with circRNAs, have demonstrated promise in preclinical studies [30].
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