Second General Surgery, Xinyu People's Hospital, Xinyu, China.
Can J Gastroenterol Hepatol. 2022 Dec 24;2022:1206134. doi: 10.1155/2022/1206134. eCollection 2022.
Hepatocellular carcinoma (HCC) is the most frequently occurring cancer and contributes to the largest number of cancer-associated deaths worldwide. Recent evidence suggests that circular RNAs (circRNAs), which are critical for HCC etiology and metastasis, are distinctly modulated in HCC. Nevertheless, the underlying mechanism of circRNA-mediated sorafenib resistance (SOR) in HCC is yet to be determined.
The hsa_circ_0006988, IGF1, and miR-15a-5p contents were quantified via ELISA and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Cell Counting Kit-8 (CCK-8) was used for the IC50 evaluation. Lastly, associations among hsa_circ_0006988, IGF1, and miR-15a-5p were validated through dual-luciferase reporter (DLR) and RNA immunoprecipitation (RIP) assays.
Herein, a new circRNA, hsa_circ_0006988, was identified, and its levels were markedly enhanced in SOR-resistant (SOR-R) HCC tissues. Functionally, hsa_circ_0006988 strongly suppressed SOR toxicity . Our examination of the signaling pathway revealed that hsa_circ_0006988 sequestered miR-15a-5p, a negative modulator of IGF1, thus suggesting that hsa_circ_0006988 deficiency diminished SOR resistance of HCC, and this action utilized the release of excess miR-15a-5p, which suppressed IGF1 levels. Moreover, miR-15a-5p overexpression reversed the hsa_circ_0006988-mediated SOR-R and enhanced IGF1 levels in HCC cells.
Hsa_circ_0006988 partly promoted the SOR-R of HCC cells through miR-15a-5p sequestering and upregulation of IGF1 levels.
肝细胞癌（HCC）是最常见的癌症，也是全球癌症相关死亡人数最多的癌症。最近的证据表明，环状 RNA（circRNA）在 HCC 的发病机制和转移中起着至关重要的作用，在 HCC 中明显受到调节。然而，circRNA 介导索拉非尼耐药（SOR）的潜在机制仍有待确定。
通过酶联免疫吸附试验（ELISA）和定量实时聚合酶链反应（qRT-PCR）分别定量 hsa_circ_0006988、IGF1 和 miR-15a-5p 的含量。细胞计数试剂盒-8（CCK-8）用于评估 IC50。最后，通过双荧光素酶报告（DLR）和 RNA 免疫沉淀（RIP）实验验证 hsa_circ_0006988、IGF1 和 miR-15a-5p 之间的关联。
在此，鉴定了一个新的 circRNA，hsa_circ_0006988，其在 SOR 耐药（SOR-R）HCC 组织中明显增强。功能上，hsa_circ_0006988 强烈抑制 SOR 毒性。我们对信号通路的研究表明，hsa_circ_0006988 结合了 miR-15a-5p，miR-15a-5p 是 IGF1 的负调节剂，这表明 hsa_circ_0006988 缺乏可降低 HCC 的 SOR 耐药性，而这种作用是通过释放过量的 miR-15a-5p 抑制 IGF1 水平来实现的。此外，miR-15a-5p 的过表达逆转了 hsa_circ_0006988 介导的 SOR-R 并增强了 HCC 细胞中的 IGF1 水平。
hsa_circ_0006988 通过 miR-15a-5p 结合和上调 IGF1 水平，部分促进了 HCC 细胞的 SOR-R。
