Department of Gastrointestinal Surgery, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiang'an District, Wuhan, 430000, Hubei Province, China.
Wuhan College of Arts and Sciences, Wuhan, 430345, Hubei Province, China.
World J Surg Oncol. 2021 Jul 31;19(1):226. doi: 10.1186/s12957-021-02334-y.
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.
探讨长链非编码 TM4SF1-AS1 在胃癌（GC）组织和细胞中的作用。
采用实时荧光定量 PCR（qRT-PCR）检测 40 例 GC 组织和相邻组织中 TM4SF1-AS1 的表达，并进行比较。采用小干扰 RNA（shRNA）下调 MKN28 和 SGC7901 GC 细胞中的 TM4SF1-AS1。将细胞分为干扰组（shTM4SF1-AS1 组）和对照组（shControl 组）。MTT 和 Transwell 试验分别用于检测两组细胞的增殖和侵袭能力，流式细胞术用于检测两组细胞的凋亡率。Western blot 检测 TM4SF1-AS1 下调后细胞上皮间质转化（EMT）过程中关键蛋白及 TM4SF1 和 PI3K-AKT 信号通路的变化。
与 shControl 组相比，shTM4SF1-AS1 组的 MKN28 和 SGC7901 细胞在 48 h 和 72 h 时的增殖明显受到抑制（均 P<0.05）。shTM4SF1-AS1 组中 MKN28 和 SGC7901 细胞的侵袭数量明显低于 shControl 组（均 P<0.05）。shTM4SF1-AS1 组 MKN28 和 SGC7901 细胞的凋亡率明显高于 shControl 组（均 P<0.05）。与 shControl 组相比，EMT 相关蛋白中 E-钙黏蛋白水平明显升高（P<0.01），而 N-钙黏蛋白、Snail 和 Twist1 水平明显降低（均 P<0.01）。沉默 LncTM4SF1-AS1 表达后，shTM4SF1-AS1 组 TM4SF1 蛋白表达水平较 shControl 组下调，PI3K-AKT 信号通路中 p-PI3K 和 p-AKT 蛋白表达水平较 shControl 组下调。
TM4SF1-AS1 在胃癌组织和细胞中表达上调。干扰并下调其表达可抑制癌细胞增殖、侵袭和 EMT，并促进凋亡。这些作用的潜在机制与沉默 TM4SF1 和 PI3K-AKT 信号通路有关。TM4SF1-AS1 可能是胃癌的潜在治疗靶点。
