环状 RNA 0000285 通过 miR-1278/FNDC3B 轴调控鼻咽癌进展。

Circ_0000285 regulates nasopharyngeal carcinoma progression through miR-1278/FNDC3B axis.

机构信息

Department of Otolaryngological, Xingtai People's Hospital, Xingtai, China.

Department of Ophthalmology, Xingtai People's Hospital, Xingtai, China.

出版信息

Hum Exp Toxicol. 2023 Jan-Dec;42:9603271221141689. doi: 10.1177/09603271221141689.

DOI:10.1177/09603271221141689

PMID:36738165

Abstract

BACKGROUND

Nasopharyngeal carcinoma (NPC) is cancer with high mortality and poor prognosis. Circular RNAs (circRNAs) have been identified in a wide variety of cancers. But the functional mechanism of circ_000285 in NPC remains unclear.

PURPOSE

To decipher the biological function and molecular mechanism of circ_000285 in NPC.

METHODS

Quantitative PCR (RT-qPCR) was applied for detecting the expression of circ_0000285, miR-1278, and FNDC3B. Western blot was used to measure the protein levels of Fibronectin type III domain containing 3B (FNDC3B), Bcl2 associated X (Bax), and B cell leukemia/lymphoma 2 (Bcl2). Cell proliferation, migration, and invasion were analyzed by colony formation, 5-ethynyl-2'-deoxyuridine (EdU), and transwell assays. Cell apoptosis was detected by flow cytometry assays. ELISA assay was used to analyze Caspase-3 activity. Bioinformatics was used to predict, and the target relationship between miR-1278 and circ_0000285 or FNDC3B was verified by luciferase reporter assay. Tumor xenograft models were established to examine how circ_0000285 functions during the mediation of NPC tumor growth in vivo.

RESULTS

Increased circ_0000285 and FNDC3B expressions, and a decreased miR-1278 expression were observed in NPC tissues and cell lines. Knockdown of circ_0000285 inhibited NPC cell proliferation, migration, invasion, and while promoting NPC cell apoptosis in vitro. Circ_0000285 knockdown-mediated anti-tumor effects in NPC cells could be largely reversed by silencing of miR-1278 or overexpression of FNDC3B. Circ_0000285 could up-regulate FNDC3B expression by sponging miR-1278 in NPC cells. Knockdown of circ_0000285 could inhibit tumor growth in vivo.

CONCLUSION

Circ_0000285 upregulates FNDC3B expression by adsorbing miR-1278 to promote NPC development.

摘要

背景

鼻咽癌（NPC）是一种死亡率和预后较差的癌症。环状 RNA（circRNAs）已在多种癌症中被发现。但是 circ_000285 在 NPC 中的功能机制尚不清楚。

目的

阐明 circ_000285 在 NPC 中的生物学功能和分子机制。

方法

采用实时定量 PCR（RT-qPCR）检测 circ_000285、miR-1278 和 Fibronectin type III domain containing 3B（FNDC3B）的表达。Western blot 检测 Fibronectin type III domain containing 3B（FNDC3B）、Bcl2 associated X（Bax）和 B cell leukemia/lymphoma 2（Bcl2）的蛋白水平。通过集落形成、5-乙炔基-2'-脱氧尿苷（EdU）和 Transwell 分析检测细胞增殖、迁移和侵袭。通过流式细胞术检测细胞凋亡。ELISA 分析检测 Caspase-3 活性。通过生物信息学预测，并用荧光素酶报告基因实验验证 miR-1278 与 circ_000285 或 FNDC3B 的靶关系。建立肿瘤异种移植模型，研究 circ_0000285 在体内介导 NPC 肿瘤生长中的作用。

结果

在 NPC 组织和细胞系中观察到 circ_0000285 和 FNDC3B 表达增加，miR-1278 表达降低。体外敲低 circ_0000285 抑制 NPC 细胞增殖、迁移、侵袭，促进 NPC 细胞凋亡。在 NPC 细胞中，circ_0000285 敲低介导的抗肿瘤作用可通过沉默 miR-1278 或过表达 FNDC3B 而被显著逆转。circ_0000285 可通过海绵吸附 miR-1278 上调 NPC 细胞中的 FNDC3B 表达。敲低 circ_0000285 可抑制体内肿瘤生长。