Department of Oral Medicine, School of Stomatology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China.
Department of Stomatology, Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4237-4244. doi: 10.3892/mmr.2018.8381. Epub 2018 Jan 5.
Aberrant microRNA (miRNA/miR) expression has been reported in various cancer types. miR‑21, which is considered to be a proto-oncogene and is frequently overexpressed in certain cancer types, has been implicated in tumorigenesis. The aim of the present study was to investigate the effect of miR‑21 degradation on tumor progression and its potential mechanisms in human salivary adenoid cystic carcinoma (SACC) development. Results of reverse transcription‑quantitative polymerase chain reaction analysis indicated that SACC cells with high metastatic potential (SACC‑LM cells) exhibited a significantly higher expression of miR‑21 compared with SACC cells with a lower metastatic potential (SACC‑83 cells). In addition, following transfection of SACC‑LM cells with miR‑21 inhibitor, cell viability was reduced, which may be a result of reduced cell proliferation and metastasis, and the induction of apoptosis, as determined by Cell Counting Kit‑8, wound healing, Matrigel invasion and flow cytometry assays. Furthermore, bioinformatics analysis indicated that programmed cell death 4 (PDCD4), phosphatase and tensin homolog deleted on chromosome ten (PTEN) and B‑cell lymphoma (Bcl)‑2 are potential target genes of miR‑21. Therefore, western blotting was performed to investigate the expression of these proteins, and the results demonstrated that miR‑21 expression level was negatively associated with PDCD4 and PTEN protein expression, and positively associated with Bcl‑2 protein expression, in SACC‑LM cells, indicating that miR‑21 may promote SACC progression via PDCD4, PTEN and Bcl‑2. In conclusion, the present study indicates that miR‑21 may be a novel target for SACC therapy and provide a novel basis for the clinical treatment of SACC.
异常的 microRNA (miRNA/miR) 表达已在各种癌症类型中报道。miR-21 被认为是原癌基因,在某些癌症类型中经常过表达,与肿瘤发生有关。本研究旨在探讨 miR-21 降解对人类涎腺腺样囊性癌 (SACC) 发展中肿瘤进展的影响及其潜在机制。逆转录-定量聚合酶链反应分析的结果表明,具有高转移潜能的 SACC 细胞 (SACC-LM 细胞) 中 miR-21 的表达明显高于具有低转移潜能的 SACC 细胞 (SACC-83 细胞)。此外,SACC-LM 细胞转染 miR-21 抑制剂后,细胞活力降低,这可能是由于细胞增殖和转移减少以及细胞凋亡诱导所致,通过 Cell Counting Kit-8、划痕愈合、Matrigel 侵袭和流式细胞术测定。此外,生物信息学分析表明,程序性细胞死亡因子 4 (PDCD4)、磷酸酶和张力蛋白同源物缺失的染色体 10 (PTEN) 和 B 细胞淋巴瘤 (Bcl)-2 是 miR-21 的潜在靶基因。因此,进行了 Western blot 以研究这些蛋白质的表达,结果表明 miR-21 的表达水平与 SACC-LM 细胞中 PDCD4 和 PTEN 蛋白表达呈负相关,与 Bcl-2 蛋白表达呈正相关,表明 miR-21 可能通过 PDCD4、PTEN 和 Bcl-2 促进 SACC 进展。综上所述,本研究表明 miR-21 可能是 SACC 治疗的新靶点,并为 SACC 的临床治疗提供了新的依据。