Long Ling, Zeng Chao, Chen Honglei, Zhou Taicheng, Wu Lili, Cai Xiaodong
Department of Neurology, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Pathology, the Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Ann Transl Med. 2020 Aug;8(15):927. doi: 10.21037/atm-20-1068.
BACKGROUND: Neural stem cells (NSCs) are undifferentiated precursor cells that have the ability to self-renew and proliferate and have the capacity to become either glia (oligodendrocytes and astrocytes) or neurons. NSCs can act as beneficial adjuncts for many neurological disorders, such as cerebral infarction, spinal cord injuries, Alzheimer's disease, and Parkinson's disease. Long noncoding RNAs (lncRNAs) play essential roles during cell differentiation, proliferation, and metabolism. This study aimed to explore the role played by adipocyte differentiation-associated long noncoding RNA (ADNCR) in the self-renewal and multipotency of NSCs. METHODS: In this study, we identified NSCs and verified that these cells were able to regenerate and differentiate into both astrocytes and neurons. Then we studied the relation between expression of ADNCR and transcription factor 3 (TCF3) and proliferation of NSCs. RESULTS: ADNCR and TCF3 expression have been shown to decrease during the differentiation of NSCs into both neurons and astrocyte induction cells. However, the expression of the microRNA miR-204-5p increased over time during the differentiation of NSCs into both neurons and astrocyte induction cells. ADNCR acts as a competing endogenous RNA (ceRNA) for miR-204-5p, and the overexpression of ADNCR suppressed miR-204-5p expression and enhanced TCF3 expression in NSCs, which resulted in enhanced proliferation and suppressed neural differentiation. CONCLUSIONS: These data suggested that the use of ADNCR may represent a new strategy for expanding the interventions used to treat neurological disorders.
背景:神经干细胞(NSCs)是未分化的前体细胞,具有自我更新和增殖能力,能够分化为神经胶质细胞(少突胶质细胞和星形胶质细胞)或神经元。神经干细胞可作为多种神经系统疾病的有益辅助手段,如脑梗死、脊髓损伤、阿尔茨海默病和帕金森病。长链非编码RNA(lncRNAs)在细胞分化、增殖和代谢过程中发挥着重要作用。本研究旨在探讨脂肪细胞分化相关长链非编码RNA(ADNCR)在神经干细胞自我更新和多能性中的作用。 方法:在本研究中,我们鉴定了神经干细胞,并证实这些细胞能够再生并分化为星形胶质细胞和神经元。然后我们研究了ADNCR的表达与转录因子3(TCF3)以及神经干细胞增殖之间的关系。 结果:在神经干细胞向神经元和星形胶质细胞诱导细胞分化过程中,ADNCR和TCF3的表达均降低。然而,在神经干细胞向神经元和星形胶质细胞诱导细胞分化过程中,微小RNA miR-204-5p的表达随时间增加。ADNCR作为miR-204-5p的竞争性内源性RNA(ceRNA),ADNCR的过表达抑制了神经干细胞中miR-204-5p的表达并增强了TCF3的表达,从而导致增殖增强和神经分化受到抑制。 结论:这些数据表明,使用ADNCR可能代表一种用于扩展治疗神经系统疾病干预措施的新策略。
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