Pan Yiyuan, Pan Yiqi, Cheng Yue, Yang Fan, Yao Zhihan, Wang Ouchen
1Department of Surgical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000 China.
2Wenzhou Medical University, Wenzhou, 325000 China.
Cell Biosci. 2018 Feb 5;8:7. doi: 10.1186/s13578-018-0207-5. eCollection 2018.
MAPT-AS1, a long non-coding RNA, has not been reported in any previous research about its function in cancers. In this study, we investigated the role of MAPT-AS1 in the progression and paclitaxel resistance in breast cancer, and the regulation between MAPT-AS1 and its natural comparable sense transcripts MAPT.
We analysed the breast cancer patients' clinical information and explored the function of MAPT-AS1 by gain- and loss-of function assays in vitro and in vivo. The regulation between MAPT-AS1 and MAPT was confirmed by gene expression analysis and rescue assays. To verify the hypothesis that MAPT-AS1 and MAPT might form a duplex structure, we performed RT-PCR assays on RNA after α-amanitin treatment.
By analysing the breast cancer patients' clinical information from the TCGA database, we found that ER-negative patients with younger age (< 60), larger tumors (≥ 2 cm), metastatic lymph nodes and stages (III-IV) had higher expression of MAPT-AS1. MAPT-AS1 is correlated with the cell growth, invasiveness and paclitaxel resistance by regulating its natural comparable sense transcripts MAPT in ER-negative breast cancer cells. The result revealed that MAPT-AS1 overexpression could partially protect the MAPT mRNA from degradation, while MAPT-AS1 knockdown decreased the stability of MAPT mRNA. Meanwhile, MAPT knockdown decreased the expression of MAPT-AS1 mRNA. MAPT-AS1 expressed coordinately with MAPT in breast tumor tissues.
Our study is the first to report a novel lncRNA MAPT-AS1 in human cancer. ER-negative patients with younger age (< 60), larger tumors (≥ 2 cm), metastatic lymph nodes and stages (III-IV) had higher expression of MAPT-AS1. MAPT-AS1 is correlated with the cell growth, invasiveness and paclitaxel resistance in ER-negative breast cancer cells through antisense pairing with MAPT. MAPT-AS1 may serve as a potential therapeutic target in ER-negative breast cancers.
长链非编码RNA MAPT-AS1在以往任何关于其在癌症中功能的研究中均未被报道。在本研究中，我们调查了MAPT-AS1在乳腺癌进展和对紫杉醇耐药中的作用，以及MAPT-AS1与其天然可比正义转录本MAPT之间的调控关系。
我们分析了乳腺癌患者的临床信息，并通过体外和体内的功能获得和功能缺失实验探究了MAPT-AS1的功能。通过基因表达分析和拯救实验证实了MAPT-AS1与MAPT之间的调控关系。为了验证MAPT-AS1和MAPT可能形成双链结构的假设，我们在α-鹅膏蕈碱处理后的RNA上进行了RT-PCR实验。
通过分析来自TCGA数据库的乳腺癌患者临床信息，我们发现年龄较小（<60岁）、肿瘤较大（≥2cm）、有转移淋巴结且处于III-IV期的雌激素受体阴性患者中MAPT-AS1表达较高。在雌激素受体阴性的乳腺癌细胞中，MAPT-AS1通过调节其天然可比正义转录本MAPT与细胞生长、侵袭性和对紫杉醇的耐药性相关。结果显示，MAPT-AS1过表达可部分保护MAPT mRNA不被降解，而MAPT-AS1敲低则降低了MAPT mRNA的稳定性。同时，MAPT敲低降低了MAPT-AS1 mRNA的表达。MAPT-AS1在乳腺肿瘤组织中与MAPT协同表达。
我们的研究首次报道了人类癌症中一种新的长链非编码RNA MAPT-AS1。年龄较小（<60岁）、肿瘤较大（≥2cm）、有转移淋巴结且处于III-IV期的雌激素受体阴性患者中MAPT-AS1表达较高。在雌激素受体阴性的乳腺癌细胞中，MAPT-AS1通过与MAPT反义配对与细胞生长、侵袭性和对紫杉醇的耐药性相关。MAPT-AS1可能是雌激素受体阴性乳腺癌的一个潜在治疗靶点。
