lncRNA LINC00346的沉默通过抑制JAK1/STAT3信号传导抑制结肠癌细胞的增殖并促进其凋亡。
Silencing of lncRNA LINC00346 Inhibits the Proliferation and Promotes the Apoptosis of Colorectal Cancer Cells Through Inhibiting JAK1/STAT3 Signaling.
作者信息
Li Dan, Wen Shuang
机构信息
Department of Pathology, Tianjin Baodi Hospital, Baodi Clinical College of Tianjin Medical University, Tianjin City 301800, People's Republic of China.
Department of Pathology, The Friendship Hospital of Dalian, Dalian City, Liaoning Province 116000, People's Republic of China.
出版信息
Cancer Manag Res. 2020 Jun 16;12:4605-4614. doi: 10.2147/CMAR.S249491. eCollection 2020.
PURPOSE
The study was aimed to investigate the effect and mechanism of lncRNA LINC00346 on cell proliferation and apoptosis of colorectal cancer (CRC).
METHODS
The expression of lncRNA LINC00346 in CRC tissues and cells was detected by qRT-PCR. LINC00346 was overexpressed and silenced in HT29 and LoVo cells by the transfection of pcDNA-LINC00346 and si-LINC00346. The proliferation of CRC cells was detected by CCK-8 and colony-formation assay. The apoptosis was detected by flow cytometry assay. The expression of apoptosis-associated proteins (Caspase-3, Bcl-2, Bax) and JAK1/STAT3 signaling-associated proteins (JAK1, STAT3, p-JAK1, p-STAT3) was detected by Western blot. The tumor growth was detected in mice subcutaneous injected with transfected HT29 cells.
RESULTS
LINC00346 was significantly upregulated in CRC tissues and cells. Overexpression of LINC00346 significantly increased the OD values, number of colonies, decreased the apoptosis rate, upregulated Bcl-2, and downregulated Caspase-3 and Bax in HT29 and LoVo cells. Knockdown of LINC00346 exerted opposite results of proliferation and apoptosis on HT29 and LoVo cells. The expression levels of JAK1/JAK1 and p-STAT3/STAT3 were upregulated by LINC00346 overexpression. Tofacitinib (JAK1 inhibitor) reversed the tumor-promoting effect of LINC00346 overexpression on CRC cells. In vivo experiments further validated that LINC00346 overexpression promoted the growth of CRC xenograft tumors.
CONCLUSION
LncRNA LINC00346 promoted the proliferation and inhibited the apoptosis of CRC cells through activating JAK1/STAT3 signaling.
目的
本研究旨在探讨长链非编码RNA LINC00346对结直肠癌（CRC）细胞增殖和凋亡的影响及其机制。
方法
采用qRT-PCR检测lncRNA LINC00346在CRC组织和细胞中的表达。通过转染pcDNA-LINC00346和si-LINC00346，在HT29和LoVo细胞中过表达和沉默LINC00346。采用CCK-8法和集落形成试验检测CRC细胞的增殖情况。通过流式细胞术检测细胞凋亡情况。采用蛋白质免疫印迹法检测凋亡相关蛋白（Caspase-3、Bcl-2、Bax）和JAK1/STAT3信号相关蛋白（JAK1、STAT3、p-JAK1、p-STAT3）的表达。对皮下注射转染HT29细胞的小鼠进行肿瘤生长检测。
结果
LINC00346在CRC组织和细胞中显著上调。LINC00346过表达显著增加了HT29和LoVo细胞的OD值、集落数，降低了凋亡率，上调了Bcl-2，下调了Caspase-3和Bax。敲低LINC00346对HT29和LoVo细胞的增殖和凋亡产生相反的结果。LINC00346过表达上调了JAK1/JAK1和p-STAT3/STAT3的表达水平。托法替布（JAK1抑制剂）逆转了LINC00346过表达对CRC细胞的促肿瘤作用。体内实验进一步证实LINC00346过表达促进了CRC异种移植瘤的生长。
结论
长链非编码RNA LINC00346通过激活JAK1/STAT3信号通路促进CRC细胞的增殖并抑制其凋亡。
Zotero 插件