Guan Yue, Li Yang, Yang Qing-Bo, Yu Jianbo, Qiao Hong
Department of Endocrinology, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Ann Transl Med. 2021 Apr;9(8):664. doi: 10.21037/atm-21-505.
LncRNAs play an important regulatory function in the occurrence and progression of papillary thyroid cancer (PTC). This study aimed to investigate the role and mechanism of ATP binding cassette subfamily C member 6 pseudogene 1 (ABCC6P1) in PTC.
Cancerous and paracancer normal thyroid tissues were collected from 18 patients with PTC, who were operated at the Second Affiliated Hospital of Harbin Medical University. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to investigate the levels of ABCC6P1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and colony formation assays. Wound healing and Transwell invasion assays were performed to examine cell migratory and invasive ability. Western blotting analysis was used to detect the expression levels of EMT-related markers and Wnt/β-catenin signaling pathway-related proteins.
The expression of ABCC6P1 was upregulated in PTC tissues and cells. ABCC6P1 silencing could significantly suppress the proliferation, colony formation ability, migratory and invasive ability in PTC cells. Moreover, knockdown of ABCC6P1 induced cell cycle arrest at G0/G1 phase and inhibited epithelial-mesenchymal transition (EMT) process of PTC cells by increasing the E-cadherin expression, but downregulating N-cadherin and vimentin expression. In addition, knockdown of ABCC6P1 caused a significant decrease in levels of Wnt/β-catenin signaling pathway members (including β-catenin, c-myc, and cyclin D1) in PTC cells.
Our study confirms that ABCC6P1 exerts an oncogenic activity in PTC which may be mediated by the Wnt/β-catenin pathway, suggesting that ABCC6P1 may be a promising therapeutic target for PTC.
长链非编码RNA在甲状腺乳头状癌（PTC）的发生和发展中发挥重要的调控作用。本研究旨在探讨ATP结合盒亚家族C成员6假基因1（ABCC6P1）在PTC中的作用及机制。
收集哈尔滨医科大学附属第二医院手术治疗的18例PTC患者的癌组织及癌旁正常甲状腺组织。采用定量逆转录聚合酶链反应（qRT-PCR）检测ABCC6P1水平。使用细胞计数试剂盒-8（CCK-8）和集落形成实验评估细胞增殖。进行伤口愈合实验和Transwell侵袭实验检测细胞迁移和侵袭能力。采用蛋白质免疫印迹分析检测上皮-间质转化（EMT）相关标志物及Wnt/β-连环蛋白信号通路相关蛋白的表达水平。
ABCC6P1在PTC组织和细胞中表达上调。ABCC6P1沉默可显著抑制PTC细胞的增殖、集落形成能力、迁移和侵袭能力。此外，敲低ABCC6P1可诱导细胞周期阻滞于G0/G1期，并通过增加E-钙黏蛋白表达、下调N-钙黏蛋白和波形蛋白表达抑制PTC细胞的上皮-间质转化（EMT）过程。另外，敲低ABCC6P1导致PTC细胞中Wnt/β-连环蛋白信号通路成员（包括β-连环蛋白、c-myc和细胞周期蛋白D1）水平显著降低。
我们的研究证实ABCC6P1在PTC中发挥致癌活性，可能由Wnt/β-连环蛋白途径介导，提示ABCC6P1可能是PTC有前景的治疗靶点。
