Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410011, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7848-7854. doi: 10.3892/mmr.2017.7520. Epub 2017 Sep 19.
It has been reported that hsa‑microRNA (miRNA/miR)‑372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa‑miR‑372 in GBC. The expression of hsa‑miR‑372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the associations between hsa‑miR‑372 expression levels and the clinicopathological characteristics of patients with GBC were determined using χ2 test. Furthermore, Kaplan‑Meier method and Cox regression analysis were performed to evaluate the association between hsa‑miR‑372 expression and the prognosis of patients with GBC. Furthermore, a dual‑luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa‑miR‑372. The results demonstrated that markedly lower hsa‑miR‑372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa‑miR‑372 was negatively associated with tumor histological grade, tumor‑node‑metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa‑miR‑372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa‑miR‑372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa‑miR‑372. In conclusion, the current study provides the first statistically convincing evidence that downregulation of hsa‑miR‑372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression.
据报道，hsa-微小 RNA（miRNA/miR）-372 在各种消化系统肿瘤中作为肿瘤抑制因子或癌基因发挥作用，但其在胆囊癌（GBC）中的作用尚未确定。本研究旨在确定 hsa-miR-372 在 GBC 中的表达及临床相关性。采用逆转录-定量聚合酶链反应检测 80 对人 GBC 组织和相邻正常胆囊组织中 hsa-miR-372 的表达。随后，采用 χ2 检验确定 hsa-miR-372 表达水平与 GBC 患者临床病理特征之间的关系。此外，采用 Kaplan-Meier 法和 Cox 回归分析评估 hsa-miR-372 表达与 GBC 患者预后的关系。此外，采用双荧光素酶报告基因检测和 Western blot 分析预测和验证 hsa-miR-372 的靶基因。结果显示，GBC 组织中 hsa-miR-372 表达明显下调，与 GBC 患者的预后不良相关。hsa-miR-372 表达下调与肿瘤组织学分级、肿瘤-淋巴结-转移分期、淋巴结转移和远处转移呈负相关，而与患者性别、年龄、肿瘤大小和胆囊结石无关。多变量 Cox 回归分析显示，hsa-miR-372 表达、组织学分级和淋巴结转移是 GBC 患者总生存期的独立预后因素。氯离子细胞内通道 1（CLIC1）先前被报道为预测 GBC 预后的有效生物标志物。值得注意的是，本研究结果表明，CLIC1 可能是 hsa-miR-372 的直接靶基因。综上所述，本研究首次提供了具有统计学说服力的证据，表明 hsa-miR-372 在 GBC 组织中可能下调，通过影响 CLIC1 表达，可能与侵袭性和进行性肿瘤行为相关。
