Department of Hepatobiliary Vascular Surgery, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Department of Pathology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Cancer Biol Ther. 2023 Dec 31;24(1):2256951. doi: 10.1080/15384047.2023.2256951. Epub 2023 Sep 29.
Hepatocellular carcinoma (HCC) is always deemed a deadly malignancy worldwide. Non-coding RNAs, including circRNAs, are becoming more widely recognized as essential regulators of the malignant development of HCC. Thus, we elaborated the regulating role of hsa_circ_0119412 in HCC advancement. The qRT-PCR was done to estimate the expressions of hsa_circ_0119412, miR-526b-5p, and Stathmin 1 (STMN1) in HCC (clinical samples and cell lines), and immunoblotting was used to detect STMN1 protein level in HCC cell lines. The stability of the circRNA was checked by processing with ribonuclease R. The proliferative potential of HCC cells was examined via the CCK-8 assay and the migratory potential by the wound healing assay. Immunoblotting was done to examine Bax and Bcl-2 (apoptosis-related proteins). Luciferase and RIP assays were employed to establish the direct interactions among miR-526b-5p and hsa_circ 0119412/STMN1. In vivo tumor growth was measured by doing a xenograft tumor experiment. In the tissues of HCC patients and cell lines derived from HCC cells, hsa_circ_0119412 was distinctly over-expressed. Knocking down hsa_circ_0119412 impeded proliferation and migration while inducing apoptosis in HCC cells. Moreover, silencing hsa_circ_0119412 diminished tumor weight and volume in vivo. Interestingly, miR-526b-5p inhibition partially restored the anti-tumor effects of silencing hsa_circ_0119412. STMN1 expression was also abundant in HCC, suggesting that it play a tumor-promoting role. Mechanistically, hsa_circ_0119412 sponged miR-526b-5p, resulting in STMN1 upregulation and thus facilitating the progression of HCC. In conclusion, this study reveals that hsa_circ_0119412 knockdown attenuates the progression of HCC by targeting miR-526b-5p/STMN1 axis.
肝细胞癌 (HCC) 在全球范围内一直被视为一种致命的恶性肿瘤。非编码 RNA，包括 circRNA，作为 HCC 恶性发展的重要调节剂，越来越受到重视。因此，我们详细阐述了 hsa_circ_0119412 在 HCC 进展中的调节作用。通过 qRT-PCR 检测 HCC（临床样本和细胞系）中 hsa_circ_0119412、miR-526b-5p 和 Stathmin 1 (STMN1) 的表达水平，并用免疫印迹法检测 HCC 细胞系中 STMN1 蛋白水平。用核糖核酸酶 R 处理检测 circRNA 的稳定性。通过 CCK-8 检测 HCC 细胞的增殖能力，通过划痕愈合检测 HCC 细胞的迁移能力。用免疫印迹法检测 Bax 和 Bcl-2（凋亡相关蛋白）。用荧光素酶和 RIP 测定法来确定 miR-526b-5p 和 hsa_circ 0119412/STMN1 之间的直接相互作用。通过进行异种移植肿瘤实验来测量体内肿瘤的生长情况。在 HCC 患者的组织和源自 HCC 细胞的细胞系中，hsa_circ_0119412 明显过表达。敲低 hsa_circ_0119412 可抑制 HCC 细胞的增殖和迁移，同时诱导细胞凋亡。此外，沉默 hsa_circ_0119412 可减少体内肿瘤的重量和体积。有趣的是，miR-526b-5p 抑制部分恢复了沉默 hsa_circ_0119412 的抗肿瘤作用。STMN1 在 HCC 中也大量表达，提示其具有促进肿瘤的作用。机制上，hsa_circ_0119412 吸附 miR-526b-5p，导致 STMN1 上调，从而促进 HCC 的进展。总之，本研究揭示了 hsa_circ_0119412 通过靶向 miR-526b-5p/STMN1 轴抑制 HCC 的进展。
