BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-codin...BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.展开更多
背景:骨的形成是一个动态的过程,破骨细胞和成骨细胞参与该动态过程。Semaphorin家族最早是作为轴突导向分子而被发现,其在许多不同组织里面表达并调节很多生理过程,近来更发现其在调节破骨细胞和成骨细胞方面发挥了重要作用。目的:总结...背景:骨的形成是一个动态的过程,破骨细胞和成骨细胞参与该动态过程。Semaphorin家族最早是作为轴突导向分子而被发现,其在许多不同组织里面表达并调节很多生理过程,近来更发现其在调节破骨细胞和成骨细胞方面发挥了重要作用。目的:总结Semaphorin家族各因子在骨动态平衡中发挥的作用。方法:应用计算机检索Pub Med和Web of science数据库中1993年6月至2014年1月关于Semaphorin家族各因子调控骨代谢的文章,以"semaphorin,sema"为检索词进行检索;排除与研究内容无关和内容重复的文章,保留48篇文章进行综述。结果与结论:semaphorins在骨的细胞生物学方面是一类新型的调控分子,研究显示semaphorins通过一些特殊的机制很活跃的参与了骨的重塑过程,semaphorin家族蛋白在骨自身动态平衡中很关键,这些发现给治疗骨质疏松、骨硬化症、关节假体旁骨溶解等骨病提供了一种新颖的方法及治疗靶点。展开更多
基金Supported by Natural Science Foundation of Hunan Province,No.2021JJ41048 and No.S2019JJQNJJ2012and Changsha Natural Science Foundation,No.kq2208400.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a prevalent malignant tumor with a poor prognosis,which is often associated with chronic hepatitis B virus infection in China.Our previous study has shown that long non-coding RNA semaphorin 6Aantisense RNA 1(SEMA6A-AS1)was significantly downregulated in hepatitis B virus-related HCC and associated with poor prognosis.AIM To explore the underlying mechanism of SEMA6A-AS1 in HCC progression.METHODS The expression levels of SEMA6A-AS1 and SEMA6A were detected using quantitative polymerase chain reaction,immunohistochemistry and Western blot.A growth curve,colony formation,wound-healing and transwell(with or without Matrigel)assays were respectively performed to assess the proliferation,migration and invasion abilities of HCC cells.Cell cycle and apoptosis assays were performed by flow cytometry.To investigate the potential mechanism underpinning SEMA6A-AS1,we utilized tagged RNA affinity purification,dual luciferase reporter assay and immunofluorescence.RESULTS Downregulation of SEMA6A-AS1 in HCC was negatively correlated with SEMA6A protein expression.SEMA6A was upregulated in HCC and correlated with high alpha-fetoprotein level,high Edmondson-Steiner grade and poor prognosis.SEMA6A-AS1 significantly inhibited the proliferation,migration and invasion of HCC cells by combining with SEMA6A mRNA and promoting its degradation.SEMA6A protein promoted the proliferation,migration and invasion of HCC cells by regulating the actin cytoskeleton.CONCLUSION Our findings suggest that SEMA6A-AS1 can inhibit HCC progression through decreasing SEMA6A expression by promoting its mRNA degradation.SEMA6A-AS1 may be a prognostic biomarker and therapeutic target for HCC.
文摘背景:骨的形成是一个动态的过程,破骨细胞和成骨细胞参与该动态过程。Semaphorin家族最早是作为轴突导向分子而被发现,其在许多不同组织里面表达并调节很多生理过程,近来更发现其在调节破骨细胞和成骨细胞方面发挥了重要作用。目的:总结Semaphorin家族各因子在骨动态平衡中发挥的作用。方法:应用计算机检索Pub Med和Web of science数据库中1993年6月至2014年1月关于Semaphorin家族各因子调控骨代谢的文章,以"semaphorin,sema"为检索词进行检索;排除与研究内容无关和内容重复的文章,保留48篇文章进行综述。结果与结论:semaphorins在骨的细胞生物学方面是一类新型的调控分子,研究显示semaphorins通过一些特殊的机制很活跃的参与了骨的重塑过程,semaphorin家族蛋白在骨自身动态平衡中很关键,这些发现给治疗骨质疏松、骨硬化症、关节假体旁骨溶解等骨病提供了一种新颖的方法及治疗靶点。
