长链非编码 RNA HOXC-AS3 过表达通过海绵吸附 miR-1269 抑制 TGF-β2 诱导的结直肠癌细胞迁移和侵袭。
LncRNA HOXC-AS3 overexpression inhibits TGF-β2-induced colorectal cancer cell migration and invasion by sponging miR-1269.
机构信息
Department of Gastrointestinal Surgery, 74725The Third Hospital of Hebei Medical University, Shijiazhuang City, Hebei Province, China.
Department of Colorectal Surgery, 70317National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Beijing City, China.
出版信息
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221093630. doi: 10.1177/09603271221093630.
OBJECTIVE
Long non-coding RNA (lncRNA HOXC-AS3 has been characterized as a cancer-related lncRNA in many types of cancer, while its role in colorectal cancer (CRC) is unknown.
METHODS
The expression of HOXC-AS3 and TGF-β2 were detected by RT-qPCR. Overexpression assays were performed to explore the interaction between HOXC-AS3 and TGF-β2. A follow-up study was performed to explore the prognostic value of HOXC-AS3 for CRC. The direct interaction between HOXC-AS3 and miR-1269 was assessed with RNA-RNA pulldown assay. Transwell assays were performed to determine the role of HOXC-AS3 and TGF-β2 in regulating CRC cell invasion and migration.
RESULTS
HOXC-AS3 was significantly downregulated in CRC tissues, while TGF-β2 was significantly upregulated in CRC tissues compared to that in adjacent non-cancer tissues of CRC patients. The follow-up study showed that low expression levels of HOXC-AS3 in CRC tissues were closely correlated with poor survival. Correlation analysis showed that HOXC-AS3 and TGF-β2 were inversely correlated across CRC tissues but not non-cancer tissues. Overexpression of HOXC-AS3 in the two cell lines resulted in downregulation of TGF-β2, while the expression of HOXC-AS3 was not affected by TGF-β2. Transwell migration and invasion assay showed that overexpression of TGF-β2 increased cell invasion and migration, while overexpression of HOXC-AS3 decreased cell migration and invasion. In addition, overexpression of HOXC-AS3 attenuated the effects of overexpression of TGF-β2. MiR-1269 increased the expression of TGF-β2. HOXC-AS3 directly interacted with miR-1269 in CRC cells.
CONCLUSIONS
Upregulation of HOXC-AS3 inhibited TGF-β2-induced colorectal cancer (CRC) cell migration and invasion possibly by sponging miR-1269.
目的
长链非编码 RNA（lncRNA）HOXC-AS3 在许多类型的癌症中被认为是一种与癌症相关的 lncRNA，而其在结直肠癌（CRC）中的作用尚不清楚。
方法
通过 RT-qPCR 检测 HOXC-AS3 和 TGF-β2 的表达。进行过表达实验以探讨 HOXC-AS3 和 TGF-β2 之间的相互作用。进行后续研究以探讨 HOXC-AS3 对 CRC 的预后价值。通过 RNA-RNA 下拉测定评估 HOXC-AS3 与 miR-1269 之间的直接相互作用。进行 Transwell 实验以确定 HOXC-AS3 和 TGF-β2 在调节 CRC 细胞侵袭和迁移中的作用。
结果
与 CRC 患者的相邻非癌组织相比，CRC 组织中 HOXC-AS3 表达显著下调，而 TGF-β2 表达显著上调。随访研究表明，CRC 组织中 HOXC-AS3 表达水平低与生存不良密切相关。相关性分析表明，CRC 组织中 HOXC-AS3 和 TGF-β2 呈负相关，但非癌组织中并非如此。在两种细胞系中过表达 HOXC-AS3 导致 TGF-β2 下调，而 TGF-β2 的表达不受 HOXC-AS3 的影响。Transwell 迁移和侵袭实验表明，过表达 TGF-β2 增加了细胞侵袭和迁移，而过表达 HOXC-AS3 降低了细胞迁移和侵袭。此外，过表达 HOXC-AS3 减弱了过表达 TGF-β2 的作用。miR-1269 增加了 TGF-β2 的表达。HOXC-AS3 在 CRC 细胞中直接与 miR-1269 相互作用。
结论
HOXC-AS3 的上调抑制了 TGF-β2 诱导的结直肠癌（CRC）细胞迁移和侵袭，可能是通过海绵吸附 miR-1269 实现的。
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