Long noncoding RNA SGO1-AS1 inactivates TGFβ signaling by facilitating TGFB1/2 mRNA decay and inhibits gastric carcinoma metastasis.
Long noncoding RNA SGO1-AS1 inactivates TGFβ signaling by facilitating TGFB1/2 mRNA decay and inhibits gastric carcinoma metastasis.
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DOI：
10.1186/s13046-021-02140-0
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发表时间：
2021-10-28
期刊：
影响因子：
--
通讯作者：
Deng M
中科院分区：
文献类型：
--
作者：
Huang D;Zhang K;Zheng W;Zhang R;Chen J;Du N;Xia Y;Long Y;Gu Y;Xu J;Deng M
尽管数以千计的长链非编码rna （lncrna）已被注释，但只有少数lncrna已被功能表征。在本研究中，我们旨在发现参与胃癌（GC）进展的新型lncrna，并探讨其在胃癌中的调控机制和临床意义。使用lncRNA表达微阵列来鉴定配对GCs与邻近正常粘膜组织之间的lncRNA表达谱差异。通过上述方法，选择lncRNA SGO1-AS1进行进一步研究。采用定量反转录聚合酶链反应（qRT-PCR）和原位杂交（ISH）检测GC组织中SGO1-AS1的表达。通过功能获得和功能缺失分析，研究SGO1-AS1在体外和体内的功能及其上下游调控机制。胃癌组织中SGO1-AS1较癌旁正常组织下调，其下调与临床分期晚期、转移情况及患者预后不良呈正相关。功能实验表明，SGO1-AS1在体外和体内均能抑制胃癌细胞的侵袭和转移。机制上，SGO1-AS1通过竞争性结合PTBP1蛋白促进TGFB1/2 mRNA衰变，导致TGFβ产生减少，从而阻止上皮到间质转化（EMT）和转移。此外，TGFβ反过来通过诱导ZEB1抑制SGO1-AS1的转录。因此，SGO1-AS1和TGFβ通过ZEB1形成双负反馈回路，调控EMT和转移。SGO1-AS1作为内源性TGFβ通路抑制剂，抑制胃癌转移，提示胃癌治疗的新潜在靶点。在线版本包含补充材料，可在10.1186/s13046-021-02140-0获得。
Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a few lncRNAs have been characterized functionally. In this study, we aimed to identify novel lncRNAs involved in the progression of gastric carcinoma (GC) and explore their regulatory mechanisms and clinical significance in GC. A lncRNA expression microarray was used to identify differential lncRNA expression profiles between paired GCs and adjacent normal mucosal tissues. Using the above method, the lncRNA SGO1-AS1 was selected for further study. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) were performed to detect SGO1-AS1 expression in GC tissues. Gain-of-function and loss-of-function analyses were performed to investigate the functions of SGO1-AS1 and its upstream and downstream regulatory mechanisms in vitro and in vivo. SGO1-AS1 was downregulated in gastric carcinoma tissues compared to adjacent normal tissues, and its downregulation was positively correlated with advanced clinical stage, metastasis status and poor patient prognosis. The functional experiments revealed that SGO1-AS1 inhibited GC cell invasion and metastasis in vitro and in vivo. Mechanistically, SGO1-AS1 facilitated TGFB1/2 mRNA decay by competitively binding the PTBP1 protein, resulting in reduced TGFβ production and, thus, preventing the epithelial-to-mesenchymal transition (EMT) and metastasis. In addition, in turn, TGFβ inhibited SGO1-AS1 transcription by inducing ZEB1. Thus, SGO1-AS1 and TGFβ form a double-negative feedback loop via ZEB1 to regulate the EMT and metastasis. SGO1-AS1 functions as an endogenous inhibitor of the TGFβ pathway and suppresses gastric carcinoma metastasis, indicating a novel potential target for GC treatment. The online version contains supplementary material available at 10.1186/s13046-021-02140-0.
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DOI：
10.1002/hep.29654
发表时间：
2018-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Liu C;Yang Z;Wu J;Zhang L;Lee S;Shin DJ;Tran M;Wang L
通讯作者：
Wang L
长非编码RNA依赖机制调节血红素生物合成和红细胞发育
影响因子：
16.6
作者：
Liu J;Li Y;Tong J;Gao J;Guo Q;Zhang L;Wang B;Zhao H;Wang H;Jiang E;Kurita R;Nakamura Y;Tanabe O;Engel JD;Bresnick EH;Zhou J;Shi L
通讯作者：
Shi L
影响因子：
50.5
作者：
Bernards, N.;Creemers, G. J.;Lemmens, V. E. P. P.
通讯作者：
Lemmens, V. E. P. P.
长非编码 RNA GAPLINC 调节 CD44 依赖性细胞侵袭性并与胃癌不良预后相关
影响因子：
11.2
作者：
Hu, Ye;Wang, Jilin;Fang, Jing-Yuan
通讯作者：
Fang, Jing-Yuan
影响因子：
11.5
作者：
Bielli, Pamela;Panzeri, Valentina;Sette, Claudio
通讯作者：
Sette, Claudio