环状RNA hsa-circ-0013561通过miR-7-5p/PDK3轴调控头颈部鳞状细胞癌的发展。

The circRNA hsa-circ-0013561 regulates head and neck squamous cell carcinoma development via the miR-7-5p/PDK3 axis.

作者信息

Tian Kaisai, Zheng Liying, Yuan Tailei, Chen Xiaoping, Chen Qun, Xue Xiaocheng, Huang Shuixian, He Weining, Jin Mingming, Zhang Yi

机构信息

Postgraduate Training Base at Shanghai Gongli Hospital, Ningxia Medical University, Shanghai, 200135, China.

Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Pudong New Area Gongli Hospital, Shanghai, 200135, China.

出版信息

Cancer Cell Int. 2024 Mar 1;24(1):91. doi: 10.1186/s12935-024-03256-x.

DOI:10.1186/s12935-024-03256-x

PMID:38429830

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10908021/

Abstract

BACKGROUND

Circular RNAs (circRNAs) belong to a class of covalently closed single stranded RNAs that have been implicated in cancer progression. Former investigations showed that hsa-circ-0013561 is abnormally expressed in head and neck squamous cell carcinoma (HNSCC). Nevertheless, the role of hsa-circ-0013561 during the progress of HNSCC still unclear.

METHODS

Present study applied FISH and qRT-PCR to examine hsa-circ-0013561 expression in HNSCC cells and tissue samples. Dual-luciferase reporter assay was employed to identify downstream targets of hsa-circ-0013561. Transwell migration, 5-ethynyl-2'-deoxyuridine incorporation, CCK8 and colony formation assays were utilized to test cell migration and proliferation. A mouse tumor xenograft model was utilized to determine the hsa-circ-0013561 roles in HNSCC progression and metastasis in vivo.

RESULTS

We found that hsa-circ-0013561 was upregulated in HNSCC tissue samples. hsa-circ-0013561 downregulation inhibited HNSCC cell proliferation and migration to promote apoptosis and G1 cell cycle arrest. The dual-luciferase reporter assay revealed that miR-7-5p and PDK3 are hsa-circ-0013561 downstream targets. PDK3 overexpression or miR-7-5p suppression reversed the hsa-circ-0013561-induced silencing effects on HNSCC cell proliferation and migration. PDK3 overexpression reversed miR-7-5p-induced effects on HNSCC cell proliferation and migration.

CONCLUSION

The findings suggest that hsa-circ-0013561 downregulation inhibits HNSCC metastasis and progression through PDK3 expression and miR-7-5p binding modulation.

摘要

背景

环状RNA（circRNAs）属于一类共价闭合的单链RNA，与癌症进展有关。先前的研究表明，hsa-circ-0013561在头颈部鳞状细胞癌（HNSCC）中异常表达。然而，hsa-circ-0013561在HNSCC进展过程中的作用仍不清楚。

方法

本研究应用荧光原位杂交（FISH）和定量逆转录聚合酶链反应（qRT-PCR）检测hsa-circ-0013561在HNSCC细胞和组织样本中的表达。采用双荧光素酶报告基因检测法鉴定hsa-circ-0013561的下游靶点。利用Transwell迁移、5-乙炔基-2'-脱氧尿苷掺入、CCK8和集落形成试验检测细胞迁移和增殖。利用小鼠肿瘤异种移植模型确定hsa-circ-0013561在体内HNSCC进展和转移中的作用。

结果

我们发现hsa-circ-0013561在HNSCC组织样本中上调。hsa-circ-0013561的下调抑制了HNSCC细胞的增殖和迁移，促进了细胞凋亡和G1期细胞周期阻滞。双荧光素酶报告基因检测显示，miR-7-5p和PDK3是hsa-circ-0013561的下游靶点。PDK3的过表达或miR-7-5p的抑制逆转了hsa-circ-0013561对HNSCC细胞增殖和迁移的沉默作用。PDK3的过表达逆转了miR-7-5p对HNSCC细胞增殖和迁移的影响。