Circular RNA circ_0001459 accelerates hepatocellular carcinoma progression via the miR‐6165/IGF1R axis

Abstract

An increasing amount of evidence shows that circular RNAs (circRNAs) have critical effects on cancer progression and development; however, the biological function and potential molecular mechanism of circRNAs in hepatocellular carcinoma (HCC) are still unclear. CircRNA sequencing was used to identify differentially expressed circRNAs between HCC tissue and adjacent normal tissue. We found that circ_0001459 expression was significantly elevated in HCC tissue and cell lines. Furthermore, in vitro and in vivo functional experiments were carried out to detect the effects of circ_0001459 on HCC growth and metastasis. Knockdown of circ_0001459 significantly inhibited the proliferation, migration, and invasion of HCC cells, whereas upregulation of circ_0001459 had the opposite effect. Moreover, bioinformatics analysis, dual-luciferase reporter assay, RNA immunoprecipitation, and fluorescence in situ hybridization assays were used to predict and verify the interaction between circ_0001459, miR-6165, and the target gene IGF1R. Downregulation of circ_0001459 decreased IGF1R expression and inhibited epithelialto-mesenchymal transition, which could be rescued by treatment with a miR-6165 inhibitor. Mechanistically, we revealed that circ_0001459 could sponge miR-6165 and induce the upregulation of its downstream target IGF1R, thus significantly promoting the progression of HCC. Therefore, circ_0001459 could be a new potential therapeutic target for HCC patients.

Research Progress of circRNAs during Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma

“…Dual-luciferase reporter assays confirmed the interaction between has_circ_0001459 and miR-6165, as well as between miR-6165 and IGF-1R. This confirmed that has_circ_0001459 can sponge miR-6165 and induce upregulation of its downstream target IGF-1R, thereby promoting invasion, migration, and EMT of HCC cells and significantly advancing the progression of HCC [30] . This suggests that has_circ_0001459 may serve as a prognostic factor and therapeutic target in hepatocellular carcinoma.…”

The pivotal role of EMT-related noncoding RNAs regulatory axes in hepatocellular carcinoma

“…In contrast, six circRNAs, circ_0003998 ( Song et al, 2020 ), circ_0101145 ( Jin et al, 2020 ), circBACH1 ( Li et al, 2021 ), circPUM1 ( Zhang et al, 2021 ), circ_0051040 ( Ju et al, 2022 ) and circ_0001459 ( Shen et al, 2022 ), have been observed to manipulate various miR/mRNA axes to induce EMT. Besides, elevated level of circSEC24A leads to the expression of protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F) and matrix metalloproteinase 3 (MMP3) by sponging miR-455-3p and miR-421, respectively ( Liao et al, 2021 ; Zhang and Zhou, 2022 ).…”

Hepatocellular Carcinoma: Up-regulated Circular RNAs Which Mediate Efficacy in PreclinicalIn VivoModels

“…Circ000149 (Figure 1) was increased in patients with HCC and promoted growth, migration, and invasion of HepG2 and Huh7 HCC cells (26). Circ0001459 promoted tumor growth and lung metastasis of these cell lines after injection into the flanks of nude mice (26). Circ0001459 sponged miR-6165 and up-regulated IGF-1R (26).…”