Circ_0039411通过介导miR-423-5p/SOX4信号通路促进甲状腺乳头状癌的发展。
Circ_0039411 promotes papillary thyroid carcinoma development through mediating the miR-423-5p/SOX4 signaling.
作者信息
Wen Xiaohui, Du Jingyan, Wang Xun
机构信息
Department of Otolarygology Head & Neck Surgery, Beijing Chao-yang Hospital, Capital Medical University, Beijing City, China.
出版信息
Int J Biol Markers. 2021 Dec;36(4):10-20. doi: 10.1177/17246008211043128. Epub 2021 Nov 5.
BACKGROUND
Papillary thyroid carcinoma is the most frequent histological subtype of thyroid cancer with a high incidence. We aimed to explore the function of circular RNA_0039411 (circ_0039411) and its associated mechanism in papillary thyroid carcinoma progression.
METHODS
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine the expression of RNA and protein, respectively. The colony formation ability, migration, invasion, and apoptosis were analyzed by colony formation assay, transwell migration assay, transwell invasion assay, and flow cytometry. Cell glycolytic metabolism was analyzed using fluorescence-based glucose assay kit and fluorescence-based lactate assay kit. Dual-luciferase reporter assay and RNA-Pull-Down Assay were performed to validate the binding between microRNA-423-5p (miR-423-5p) and circ_0039411 or SRY-box transcription factor 4 (SOX4). The xenograft tumor model was used to assess the role of circ_0039411 in the tumor growth in vivo.
RESULTS
Circ_0039411 was highly expressed in papillary thyroid carcinoma tissues and cell lines compared with adjacent normal tissues and NTHY-ORI3.1 cells. Circ_0039411 interference suppressed the colony formation ability, migration, invasion, and glycolysis but promoted the apoptosis of papillary thyroid carcinoma cells. MiR-423-5p was a target of circ_0039411 in papillary thyroid carcinoma cells. Circ_0039411 knockdown-mediated effects in papillary thyroid carcinoma cells were largely overturned by the silence of miR-423-5p. MiR-423-5p bound to the 3' untranslated region (3'UTR) of SOX4. SOX4 overexpression largely reversed circ_0039411 silencing-mediated effects in papillary thyroid carcinoma cells. Circ_0039411 positively regulated SOX4 expression by sponging miR-423-5p in papillary thyroid carcinoma cells. Circ_0039411 silencing notably suppressed the growth of xenograft tumors in vivo.
CONCLUSION
Circ_0039411 promoted the malignant behaviors of papillary thyroid carcinoma cells partly depending on the regulation of the miR-423-5p/SOX4 axis.
背景
甲状腺乳头状癌是甲状腺癌中最常见的组织学亚型，发病率较高。我们旨在探讨环状RNA_0039411（circ_0039411）在甲状腺乳头状癌进展中的作用及其相关机制。
方法
分别采用逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测RNA和蛋白质的表达。通过集落形成试验、Transwell迁移试验、Transwell侵袭试验和流式细胞术分析细胞的集落形成能力、迁移、侵袭和凋亡情况。使用基于荧光的葡萄糖检测试剂盒和基于荧光的乳酸检测试剂盒分析细胞糖酵解代谢。进行双荧光素酶报告基因试验和RNA下拉试验，以验证微小RNA-423-5p（miR-423-5p）与circ_0039411或SRY盒转录因子4（SOX4）之间的结合。采用异种移植瘤模型评估circ_0039411在体内肿瘤生长中的作用。
结果
与癌旁正常组织和NTHY-ORI3.1细胞相比，circ_0039411在甲状腺乳头状癌组织和细胞系中高表达。circ_0039411干扰抑制了甲状腺乳头状癌细胞的集落形成能力、迁移、侵袭和糖酵解，但促进了细胞凋亡。miR-423-5p是甲状腺乳头状癌细胞中circ_0039411的靶标。miR-423-5p沉默在很大程度上逆转了circ_0039411敲低介导的对甲状腺乳头状癌细胞的影响。miR-423-5p与SOX4的3'非翻译区（3'UTR）结合。SOX4过表达在很大程度上逆转了circ_0039411沉默介导的对甲状腺乳头状癌细胞的影响。在甲状腺乳头状癌细胞中，circ_0039411通过海绵吸附miR-423-5p正向调节SOX4表达。circ_0039411沉默显著抑制了体内异种移植瘤的生长。
结论
circ_0039411促进甲状腺乳头状癌细胞的恶性行为，部分依赖于对miR-423-5p/SOX4轴的调控。
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