Effect and mechanism of downregulating the long-chain noncoding RNA TM4SF1-AS1 on the proliferation, apoptosis and invasion of gastric cancer cells.
Effect and mechanism of downregulating the long-chain noncoding RNA TM4SF1-AS1 on the proliferation, apoptosis and invasion of gastric cancer cells.
复制标题
DOI：
10.1186/s12957-021-02334-y
复制
发表时间：
2021-07-31
影响因子：
3.2
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
He C;Qi W;Wang Z
目的研究胃癌组织和细胞中长链非编码基因TM4SF1-AS1。采用实时荧光定量聚合酶链式反应(qRT-PCR)检测40例胃癌组织及癌旁组织中TM4SF1-AS1的表达，并进行比较。利用小干扰RNA(ShRNA)下调MKN28和SGC7901胃癌细胞TM4SF1-AS1的表达。将细胞分为干预组(shTM4SF1-AS1组)和对照组(shControl组)。用四甲基偶氮唑盐比色法和Transwell法检测两组细胞的增殖和侵袭能力，并用流式细胞仪检测两组细胞的凋亡率。Western blotting检测细胞上皮向间充质转化(EMT)过程中关键蛋白的变化，以及TM4SF1和PI3K-AKT信号通路对TM4SF1-AS1下调的响应。与shControl组相比，shTM4SF1-AS1组48h和72hMKN28和SGC7901细胞的增殖均受到明显抑制(均P< ； <0.05)。ShTM4SF1-AS1组侵袭的MKN28和SGC7901细胞数明显低于shControl组(均P< ； <0.05)。MKN28和SGC7901shTM4SF1-AS1组细胞凋亡率明显高于shControl组(均P< ； <0.05)。与假手术对照组相比，E-钙粘蛋白在EMT相关蛋白中的表达显著升高(P <； )，而N-钙粘蛋白、蜗牛和Twist1的表达显著降低(均P <； )。抑制LncTM4SF1-AS1表达后，shTM4SF1-AS1组TM4SF1表达水平较shControl组下调，PI3K-AKT信号通路中p-PI3K和p-AKT蛋白表达较shControl组下调。TM4SF1-AS1在胃癌组织和细胞中表达上调。干扰和下调其表达可抑制癌细胞的增殖、侵袭和EMT，促进细胞凋亡。这些效应的潜在机制与沉默TM4SF1和PI3K-AKT信号通路有关。TM4SF1-AS1可能成为胃癌治疗的潜在靶点。
To investigate long-chain noncoding TM4SF1-AS1 in gastric cancer (GC) tissues and cells. TM4SF1-AS1 in 40 GC tissues and adjacent tissues was detected and compared using real-time fluorescence quantitative PCR (qRT-PCR). TM4SF1-AS1 in MKN28 and SGC7901 GC cells was downregulated using small interfering RNA (shRNA). The cells were grouped into an interference group (shTM4SF1-AS1 group) and a control group (shControl group). MTT and Transwell tests were applied to determine the proliferation and invasion of the cells in both groups, and flow cytometry was performed to assess the apoptosis rate in the two groups. Western blotting was performed to determine changes in key proteins in cells during the epithelial-to-mesenchymal transition (EMT) and in the TM4SF1 and PI3K-AKT signalling pathways in response to the downregulation of TM4SF1-AS1. The proliferation of MKN28 and SGC7901 in the shTM4SF1-AS1 group was significantly inhibited at 48 h and 72 h compared to that in the shControl group (all P < 0.05). In the shTM4SF1-AS1 group, the number of invaded MKN28 and SGC7901 cells was significantly lower than that in the shControl group (all P < 0.05). Apoptosis in the MKN28 and SGC7901 shTM4SF1-AS1 groups was significantly higher than that in the shControl group (all P < 0.05). Compared to those in the shControl group, levels of E-cadherin in EMT-related proteins were significantly elevated (P < 0.01), while levels of N-cadherin, Snail and Twist1 were significantly decreased (all P < 0.01). After silencing the expression of LncTM4SF1-AS1, the expression levels of TM4SF1 in the shTM4SF1-AS1 group were downregulated compared to those in the shControl group, and the p-PI3K and p-AKT proteins in the PI3K-AKT signalling pathway in the shTM4SF1-AS1 group were downregulated compared to those of the shControl group. TM4SF1-AS1 is upregulated in gastric cancer tissues and cells. Interfering with and downregulating its expression inhibit cancer cell proliferation, invasion and the EMT and promote apoptosis. The underlying mechanism for these effects is related to silencing the TM4SF1 and PI3K-AKT signalling pathways. TM4SF1-AS1 may be a potential therapeutic target for gastric cancer.
登录
查看更多内容
胃癌来源的间充质基质细胞触发M2巨噬细胞极化，促进胃癌转移和EMT
影响因子：
9
作者：
Li, Wei;Zhang, Xu;Zhao, Shaolin
通讯作者：
Zhao, Shaolin
影响因子：
2.2
作者：
Ding, Xiaoqian;Wang, Qiang;Sun, Yong
通讯作者：
Sun, Yong
影响因子：
4
作者：
Leng, Xue;Liu, Geli;Song, Fangzhou
通讯作者：
Song, Fangzhou
影响因子：
4.3
作者：
Zhang, Yangmei;Yuan, Yuan;Chen, Kai
通讯作者：
Chen, Kai
影响因子：
--
作者：
Hao NB;He YF;Li XQ;Wang K;Wang RL
通讯作者：
Wang RL