Department of Otorhinolaryngology, Qilu Hospital, Shandong University, Key Laboratory of Otolaryngology, NHFPC (Shandong University), Shandong, China.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
J Cell Mol Med. 2020 Apr;24(8):4687-4697. doi: 10.1111/jcmm.15134. Epub 2020 Mar 12.
Increasing number of circular RNAs (circRNAs) have been reported to play important role in gene regulation, carcinogenesis and pathogenesis in various cancers. However, the biological functions and underlying molecular mechanisms of circRNAs in hypopharyngeal squamous cell carcinoma (HSCC) remain elusive. Thus, secondary circRNA-seq profiling was performed to identify the differentially expressed circRNAs between HSCC tissues and adjacent normal tissues, and the expression level of circMATR3 (derived from human gene matrin3 (MATR3), has_circRNA_0008922) was confirmed by qRT-PCR. Proliferation of HSCC cells was detected by cell counting kit-8 (CCK8) assay, apoptosis and the cell cycle were analysed by flow cytometry, and the migration and invasion of HSCC cells was determined by transwell assay. Bioinformatics analysis was conducted to predict possible pathways and potential miRNA targets of circMATR3. We found that circMATR3 was up-regulated in HSCC tissues, and abundant circMATR3 expression was markedly correlated with late T classification, advanced clinical stage, greater lymph node metastasis, and poor prognosis. Furthermore, knock-down of circMATR3 significantly inhibited proliferation, migration and invasion of HSCC cells, whereas silencing of circMATR3 induced cell apoptosis. Our analysis predicted that circMATR3 may participate in cancer-related pathways by serving as miRNA sponges. In conclusion, our findings first identified the oncogenic roles of circMATR3 in promoting the progression of HSCC and demonstrated that circMATR3 may be a novel prognostic marker and therapeutic target for HSCC.
越来越多的环状 RNA(circRNAs)被报道在各种癌症中的基因调控、致癌作用和发病机制中发挥重要作用。然而,circRNAs 在下咽鳞状细胞癌(HSCC)中的生物学功能和潜在分子机制仍不清楚。因此,进行了二次 circRNA-seq 分析,以鉴定 HSCC 组织和相邻正常组织之间差异表达的 circRNAs,并通过 qRT-PCR 验证 circMATR3(来源于人类基因 matrin3(MATR3),has_circRNA_0008922)的表达水平。通过细胞计数试剂盒-8(CCK8)测定 HSCC 细胞的增殖,通过流式细胞术分析细胞凋亡和细胞周期,通过 Transwell 测定 HSCC 细胞的迁移和侵袭。进行生物信息学分析以预测 circMATR3 的可能途径和潜在 miRNA 靶标。我们发现 circMATR3 在 HSCC 组织中上调,丰富的 circMATR3 表达与晚期 T 分类、晚期临床分期、更大的淋巴结转移和不良预后显著相关。此外,circMATR3 的敲低显著抑制 HSCC 细胞的增殖、迁移和侵袭,而 circMATR3 的沉默诱导细胞凋亡。我们的分析预测,circMATR3 可能通过作为 miRNA 海绵参与癌症相关途径。总之,我们的研究结果首次确定了 circMATR3 在促进 HSCC 进展中的致癌作用,并表明 circMATR3 可能是 HSCC 的一种新的预后标志物和治疗靶点。