Hsa_circ_0119412 is a tumor promoter in hepatocellular carcinoma by inhibiting miR-526b-5p to upregulate STMN1.

IF 4.4 4区 医学 Q2 ONCOLOGY
Cancer Biology & Therapy Pub Date : 2023-12-31 Epub Date: 2023-09-29 DOI:10.1080/15384047.2023.2256951
Song Wu, Tao Tang, Hongchi Zhou, Jing Huang, Xiaoliang Kang, Junli Zhang
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引用次数: 0

Abstract

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.

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Hsa_cir_0119412是肝细胞癌的肿瘤启动子,通过抑制miR-526b-5p上调STMN1。
肝细胞癌一直被认为是一种致命的恶性肿瘤。非编码RNA,包括circRNA,越来越被广泛认为是HCC恶性发展的重要调节因子。因此,我们详细阐述了hsa_cir_0119412在HCC进展中的调节作用。qRT-PCR用于评估hsa_cir_0119412、miR-526b-5p和Stathmin 1(STMN1)在HCC(临床样品和细胞系)中的表达,并使用免疫印迹检测HCC细胞系中的STMN1蛋白水平。通过用核糖核酸酶R处理检查circRNA的稳定性。通过CCK-8测定检测HCC细胞的增殖潜力,通过伤口愈合测定检测迁移潜力。免疫印迹法检测Bax和Bcl-2(凋亡相关蛋白)。使用萤光素酶和RIP测定来建立miR-526b-5p和hsa_cir0119412/STMN1之间的直接相互作用。通过进行异种移植物肿瘤实验来测量体内肿瘤生长。在HCC患者的组织和来源于HCC细胞的细胞系中,hsa_cir_0119412明显过表达。敲除hsa_cir_0119412阻碍HCC细胞的增殖和迁移,同时诱导细胞凋亡。此外,沉默hsa_cir_0119412降低了体内肿瘤的重量和体积。有趣的是,miR-526b-5p的抑制部分恢复了沉默hsa_cir_0119412的抗肿瘤作用。STMN1在HCC中也有丰富的表达,表明其具有促肿瘤作用。从机制上讲,hsa_cir_0119412吸收miR-526b-5p,导致STMN1上调,从而促进HCC的进展。总之,本研究表明,hsa_cir_0119412敲低通过靶向miR-526b-5p/STMN1轴来减轻HCC的进展。
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来源期刊
Cancer Biology & Therapy
Cancer Biology & Therapy 医学-肿瘤学
CiteScore
7.00
自引率
0.00%
发文量
60
审稿时长
2.3 months
期刊介绍: Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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