Department of Thyroid Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, 510030, China.
Department of Operating room, Sun Yat-Sen Memorial Hospital, Guangzhou, Guangdong, 510030, China.
Pathol Res Pract. 2021 May;221:153395. doi: 10.1016/j.prp.2021.153395. Epub 2021 Mar 4.
The incidence of papillary thyroid cancer (PTC) has experienced a rapid increase in recent years. Long non-coding RNA-homo sapiens HLA complex group (HCG) 18 plays a regulatory role in cancers, but its role in PTC remained unknown. This study determined the expressions of HCG18, microRNA (miR)-106a-5p, and protein phosphatase 2 regulatory subunit B alpha (PPP2R2A) in PTC tissues and cells by qRT-PCR. ENCORI predicted the targeting relation between HCG18 and miR-106a-5p. TargetScan v7.2 predicted the targeting relation between miR-106a-5p and PPP2R2A. Dual-luciferase reporter assay was performed to validate the two targeting relations. The viability, migration, and invasion of PTC cells were detected by Cell Counting Kit-8, wound healing assay, and Transwell assay, respectively. The expressions of matrix metalloproteinase 2 (MMP-2), MMP-9, E-cadherin, N-cadherin, and Vimentin in TPC-1 and MDA-T68 cells were assessed by qRT-PCR and Western blot. It was found that HCG18 was down-regulated in PTC. Overexpressing HCG18 suppressed viability, migration, and invasion, promoted apoptosis, and inhibited miR-106a-5p expression in PTC cells. HCG18 interacted with miR-106a-5p, the expression of which was upregulated in PTC. Upregulating miR-106a-5p expression by lentivirus infection promoted viability, migration and invasion and inhibited apoptosis of PTC cells, reversed the effect of HCG18 on the biological behaviors of PTC cells, and promoted the expressions of MMP-2, MMP-9, E-cadherin, and Vimentin and downregulated E-cadherin expression in PTC cells. PPP2R2A, a direct target of miR-106a-5p, was downregulated in PTC, and HCG18 promoted PPP2R2A expression in PTC cells by sponging miR-106a-5p. Furthermore, PPP2R2A reversed the effects of miR-106a-5p on PTC cells. In conclusion, HCG18 suppressed viability, migration, invasion and epithelial-mesenchymal transition and promoted apoptosis of PTC cells via regulating the miR-106a-5p/PPP2R2A axis.
甲状腺乳头状癌（PTC）的发病率近年来迅速上升。长链非编码 RNA-人类 HLA 复合体组（HCG）18 在癌症中发挥调节作用，但它在 PTC 中的作用尚不清楚。本研究通过 qRT-PCR 测定了 PTC 组织和细胞中 HCG18、微小 RNA（miR）-106a-5p 和蛋白磷酸酶 2 调节亚基 Bα（PPP2R2A）的表达。ENCORI 预测了 HCG18 与 miR-106a-5p 之间的靶向关系。TargetScan v7.2 预测了 miR-106a-5p 与 PPP2R2A 之间的靶向关系。双荧光素酶报告基因实验验证了这两个靶向关系。通过细胞计数试剂盒-8、划痕愈合实验和 Transwell 实验分别检测 PTC 细胞的活力、迁移和侵袭。通过 qRT-PCR 和 Western blot 检测 TPC-1 和 MDA-T68 细胞中基质金属蛋白酶 2（MMP-2）、MMP-9、E-钙粘蛋白、N-钙粘蛋白和波形蛋白的表达。结果发现，HCG18 在 PTC 中下调。过表达 HCG18 抑制 PTC 细胞活力、迁移和侵袭，促进凋亡，抑制 miR-106a-5p 表达。HCG18 与 miR-106a-5p 相互作用，后者在 PTC 中上调。通过慢病毒感染上调 miR-106a-5p 表达促进 PTC 细胞活力、迁移和侵袭，抑制凋亡，逆转 HCG18 对 PTC 细胞生物学行为的影响，并促进 MMP-2、MMP-9、E-钙粘蛋白和波形蛋白的表达，下调 PTC 细胞中 E-钙粘蛋白的表达。PPP2R2A 是 miR-106a-5p 的直接靶标，在 PTC 中下调，HCG18 通过海绵 miR-106a-5p 促进 PTC 细胞中 PPP2R2A 的表达。此外，PPP2R2A 逆转了 miR-106a-5p 对 PTC 细胞的影响。总之，HCG18 通过调节 miR-106a-5p/PPP2R2A 轴抑制 PTC 细胞活力、迁移、侵袭和上皮-间充质转化，促进凋亡。
