微小 RNA-130a-3p 通过靶向 PSME3 下调 KPNB1 抑制甲状腺乳头状癌的进展。
MicroRNA-130a-3p impedes the progression of papillary thyroid carcinoma through downregulation of KPNB1 by targeting PSME3.
机构信息
Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, P.R. China.
Department of Endocrinology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, P.R. China.
出版信息
Endocrine. 2023 Oct;82(1):96-107. doi: 10.1007/s12020-023-03383-x. Epub 2023 May 11.
BACKGROUND
Papillary thyroid carcinoma (PTC) is the main type of thyroid cancer (THCA). Despite the good prognosis, some PTC patients may deteriorate into more aggressive disease, leading to poor survival. Our study aimed to explore the role of microRNA (miR)-130a-3p in regulating PTC.
METHODS
After transfection with miR-130a-3p-mimic, OE-PSME3, or miR-130a-3p-mimic + OE-KPNB1 in PTC cells (TPC-1), CCK-8, Transwell, scratch, and flow cytometry experiments were performed to analyze TPC-1 cell proliferation, invasion, migration, and apoptosis. Western blotting was used to detect proliferation or invasion-related protein markers (PCNA, E-cadherin, and N-cadherin). The RNA22 database, dual-luciferase reporter assay, and RNA pull-down assay were applied for the prediction and verification of the binding site between miR-130a-3p and PSME3. Pan-cancer software identified a positive correlation between PSME3 and KPNB1 in THCA. Co-immunoprecipitation was utilized to verify the interaction of PSME3 with KPNB1. Nude mice were transplanted with TPC-1 cells overexpressing miR-130a-3p. The tumors were isolated for detection of the expression of miR-130a-3p, PSME3, KPNB1, Ki-67, and CD31.
RESULTS
miR-130a-3p was lowly expressed in PTC cell lines. Upregulation of miR-130a-3p repressed the expression of PSME3 and KPNB1 and reduced the malignancy of TPC-1 cells in vitro, shown by inhibited cell proliferation, invasion, migration, and the expression of PCNA and N-cadherin. Also, overexpressed miR-130a-3p inhibited the growth of xenograft tumors in nude mice. miR-130a-3p bound to PSME3 which interacted with KPNB1.
CONCLUSION
miR-130a-3p impedes the progression of PTC by downregulating PSME3/KPNB1.
背景
甲状腺癌（THCA）主要以甲状腺乳头状癌（PTC）为主。尽管预后良好，但部分 PTC 患者病情可能恶化，发展为侵袭性更强的疾病，导致生存状况较差。本研究旨在探讨微小 RNA（miR）-130a-3p 在调控 PTC 中的作用。
方法
在 PTC 细胞（TPC-1）中转染 miR-130a-3p-模拟物、OE-PSME3 或 miR-130a-3p-模拟物+OE-KPNB1 后，通过 CCK-8、Transwell、划痕和流式细胞术实验分析 TPC-1 细胞的增殖、侵袭、迁移和凋亡。Western blot 用于检测与增殖或侵袭相关的蛋白标志物（PCNA、E-钙黏蛋白和 N-钙黏蛋白）。应用 RNA22 数据库、双荧光素酶报告基因检测和 RNA 下拉实验预测和验证 miR-130a-3p 与 PSME3 之间的结合位点。泛癌软件分析 THCA 中 PSME3 与 KPNB1 呈正相关。通过免疫共沉淀验证 PSME3 与 KPNB1 的相互作用。将过表达 miR-130a-3p 的 TPC-1 细胞移植入裸鼠体内，分离肿瘤，检测 miR-130a-3p、PSME3、KPNB1、Ki-67 和 CD31 的表达。
结果
PTC 细胞系中 miR-130a-3p 表达水平较低。miR-130a-3p 的上调抑制了 PSME3 和 KPNB1 的表达，减少了 TPC-1 细胞的体外恶性程度，表现为细胞增殖、侵袭、迁移以及 PCNA 和 N-钙黏蛋白表达的抑制。此外，过表达 miR-130a-3p 抑制了裸鼠异种移植瘤的生长。miR-130a-3p 与 PSME3 结合，而 PSME3 与 KPNB1 相互作用。
结论
miR-130a-3p 通过下调 PSME3/KPNB1 抑制 PTC 的进展。
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