Department of Pathology, CHA University College of Medicine, Seongnam 13496, Gyeonggi-do, Korea.
Institute of Clinical Research, CHA University College of Medicine, Seongnam 13496, Gyeonggi-do, Korea.
Int J Mol Sci. 2022 May 17;23(10):5623. doi: 10.3390/ijms23105623.
Alteration in expression of miRNAs can cause various malignant changes and the metastatic process. Our aim was to identify the miRNAs involved in cervical squamous cell carcinoma (SqCC) and metastasis, and to test their utility as indicators of metastasis and survival. Using microarray technology, we performed miRNA expression profiling on primary cervical SqCC tissue (n = 6) compared with normal control (NC) tissue and compared SqCC that had (SqC-M; n = 3) and had not (SqC-NM; n = 3) metastasized. Four miRNAs were selected for validation by qRT-PCR on 29 SqC-NM and 27 SqC-M samples, and nine metastatic lesions (ML-SqC), from a total of 56 patients. Correlation of miRNA expression and clinicopathological parameters was analyzed to evaluate the clinical impact of candidate miRNAs. We found 40 miRNAs differentially altered in cervical SqCC tissue: 21 miRNAs were upregulated and 19 were downregulated (≥2-fold, p < 0.05). Eight were differentially altered in SqC-M compared with SqC-NM samples: four were upregulated (miR-494, miR-92a-3p, miR-205-5p, and miR-221-3p), and four were downregulated (miR-574-3p, miR-4769-3p, miR-1281, and miR-1825) (≥1.5-fold, p < 0.05). MiR-22-3p might be a metastamiR, which was gradually further downregulated in SqC-NM > SqC-M > ML-SqC. Downregulation of miR-30e-5p significantly correlated with high stage, lymph node metastasis, and low survival rate, suggesting an independent poor prognostic factor.
miRNA 表达的改变可导致各种恶性变化和转移过程。我们的目的是鉴定参与宫颈鳞状细胞癌 (SqCC) 和转移的 miRNA,并检验它们作为转移和生存指标的效用。我们使用微阵列技术对 6 例原发性宫颈 SqCC 组织(n = 6)与正常对照(NC)组织进行 miRNA 表达谱分析,并对有转移(SqC-M;n = 3)和无转移(SqC-NM;n = 3)的 SqCC 进行比较。选择 4 个 miRNA 进行 qRT-PCR 验证,共对 29 例 SqC-NM 和 27 例 SqC-M 样本以及 56 例患者的 9 个转移病灶(ML-SqC)进行了验证。分析 miRNA 表达与临床病理参数的相关性,以评估候选 miRNA 的临床影响。我们发现 40 个 miRNA 在宫颈 SqCC 组织中差异表达:21 个上调,19 个下调(≥2 倍,p < 0.05)。SqC-M 与 SqC-NM 样本相比,有 8 个 miRNA 差异表达:4 个上调(miR-494、miR-92a-3p、miR-205-5p 和 miR-221-3p),4 个下调(miR-574-3p、miR-4769-3p、miR-1281 和 miR-1825)(≥1.5 倍,p < 0.05)。miR-22-3p 可能是一种转移 miRNA,在 SqC-NM>SqC-M>ML-SqC 中逐渐进一步下调。miR-30e-5p 的下调与高分期、淋巴结转移和低生存率显著相关,提示其为独立的不良预后因素。