Backgrounds LncRNA Brain Cytoplasmic RNA 1 (BCYRN1) has been certified to modulate cancer cells growth and aggressiveness in several tumors. However, research about function of BCYRN1 in hepatocellular carcinoma (HCC) is limited. Therefore, our research intends to explore the function of BCYRN1 in HCC. Methods HepG2 and BEL-7402 cell lines were employed for later function experiments. Differently expression levels of BCYRN1, miR-490-3p, and POU class 3 homeobox 2 (POU3F2) were determined on the base of TCGA dataset including 375 HCC patients and 50 normal. 370 cases of patients, which have fairly complete clinical data, were utilized for survival analysis of BCYRN1, miR-490-3p, or POU3F2 by Kaplan-Meier method. Relative expression pattern of BCYRN1 was examined by quantitative real time polymerase chain reaction (qRT-PCR), and relative expression level of POU3F2 was assessed by qRT-PCR and western blot. Cell biological behaviors were analyzed by cell counting kit-8, cloning formation, and transwell assays. Bioinformatics software and dual luciferase assay were applied to predict and confirm the targeted relationship between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2. Further associations among BCYRN1, miR-490-3p, and POU3F2 were analyzed by rescue assays. Results Our results exhibited that BCYRN1 was over expressed in HCC samples, which was connected with unfavorable prognosis in HCC patients. In addition, a series of experiments exhibited that overexpression of BCYRN1 significantly expedited HCC cells growth, clone formation, and movement abilities, and vice versa. Moreover, targeted relationships between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2 were affirmed by dual luciferase assay. Furthermore, POU3F2 expression was negatively connected with the expression of miR-490-3p and positively associated with BCYRN1 expression. Whilst, either overexpression of miR-490-3p or knockdown of POU3F2 could remarkably inhibit the increasing trends of proliferation, clone formation, invasion, and migration abilities induced by BCYRN1 in HCC cells. Conclusions BCYRN1, served as a competing endogenous RNA, up-regulated the expression of POU3F2 to promote the development of HCC through sponging miR-490-3p, supplying novel molecular targets and underlying prognostic biomarkers for HCC therapy.

中文翻译：

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LncRNA BCYRN1/miR-490-3p/POU3F2 作为 ceRNA 网络，与肝细胞癌患者较差的生存率相关，并促进肿瘤细胞生长和转移。

背景 LncRNA 脑细胞质 RNA 1 (BCYRN1) 已被证明可调节癌细胞在几种肿瘤中的生长和侵袭性。然而，关于 BCYRN1 在肝细胞癌 (HCC) 中的功能的研究有限。因此，我们的研究旨在探索 BCYRN1 在 HCC 中的功能。方法采用HepG2和BEL-7402细胞系进行后期功能实验。基于 TCGA 数据集（包括 375 名 HCC 患者和 50 名正常人）确定 BCYRN1、miR-490-3p 和 POU 3 类同源框 2 (POU3F2) 的不同表达水平。370例临床资料比较完整的患者，采用Kaplan-Meier法对BCYRN1、miR-490-3p或POU3F2进行生存分析。通过定量实时聚合酶链反应（qRT-PCR）检查 BCYRN1 的相对表达模式，通过qRT-PCR和蛋白质印迹评估POU3F2的相对表达水平。通过细胞计数试剂盒 8、克隆形成和 transwell 测定分析细胞生物学行为。应用生物信息学软件和双荧光素酶测定来预测和确认 BCYRN1 和 miR-490-3p 以及 miR-490-3p 和 POU3F2 之间的靶向关系。BCYRN1、miR-490-3p 和 POU3F2 之间的进一步关联通过救援分析进行了分析。结果 我们的研究结果表明，BCYRN1 在 HCC 样本中过度表达，这与 HCC 患者的不良预后有关。此外，一系列实验表明 BCYRN1 的过表达显着加快了 HCC 细胞的生长、克隆形成和运动能力，反之亦然。此外，BCYRN1 和 miR-490-3p 之间的靶向关系，以及通过双荧光素酶测定确认了miR-490-3p和POU3F2。此外，POU3F2 的表达与 miR-490-3p 的表达呈负相关，与 BCYRN1 的表达呈正相关。同时，过表达 miR-490-3p 或敲低 POU3F2 可以显着抑制 BCYRN1 在 HCC 细胞中诱导的增殖、克隆形成、侵袭和迁移能力的增加趋势。结论 BCYRN1 作为一种竞争性内源性 RNA，通过海绵状 miR-490-3p 上调 POU3F2 的表达以促进 HCC 的发展，为 HCC 治疗提供新的分子靶点和潜在的预后生物标志物。POU3F2的表达与miR-490-3p的表达呈负相关，与BCYRN1的表达呈正相关。同时，过表达 miR-490-3p 或敲低 POU3F2 可以显着抑制 BCYRN1 在 HCC 细胞中诱导的增殖、克隆形成、侵袭和迁移能力的增加趋势。结论 BCYRN1 作为一种竞争性内源性 RNA，通过海绵状 miR-490-3p 上调 POU3F2 的表达以促进 HCC 的发展，为 HCC 治疗提供新的分子靶点和潜在的预后生物标志物。POU3F2的表达与miR-490-3p的表达呈负相关，与BCYRN1的表达呈正相关。同时，过表达 miR-490-3p 或敲低 POU3F2 可以显着抑制 BCYRN1 在 HCC 细胞中诱导的增殖、克隆形成、侵袭和迁移能力的增加趋势。结论 BCYRN1 作为一种竞争性内源性 RNA，通过海绵状 miR-490-3p 上调 POU3F2 的表达以促进 HCC 的发展，为 HCC 治疗提供新的分子靶点和潜在的预后生物标志物。