Department of Surgical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, P.R. China.
Department of Rheumatism and Immunology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shannxi 710061, P.R. China.
Oncol Rep. 2020 Nov;44(5):1971-1984. doi: 10.3892/or.2020.7751. Epub 2020 Sep 4.
The KIAA0101 protein (also referred to as NS5ATP9 or Paf15) is overexpressed in esophageal squamous cell carcinoma (ESCC) and is associated with disease progression and poor patient survival, but how KIAA0101 expression is regulated remains unknown. The relationship between tumor miR‑216a‑5p expression and prognosis in patients with ESCC was revealed by survival analyses. Quantitative reverse‑transcriptase PCR and western blot analysis were used to evaluate miR‑216a‑5p and KIAA0101 expression in human ESCC tissues and cell lines. The targeting of KIAA0101 by miR‑216a‑5p was verified by dual‑luciferase reporter assays. The EC9706 and TE1 cell lines were transfected with miR‑216a‑5p mimics and inhibitor, or KIAA0101‑specific shRNA and KIAA0101‑expressing plasmids, in order to evaluate the effect of manipulating miR‑216a‑5p and KIAA0101 expression on ESCC cell proliferation, cell cycle progression, migration, and invasion. miR‑216a‑5p was lowly expressed and inversely correlated with KIAA0101 protein expression in ESCC tissues and cell lines. Lower miR‑216a‑5p expression was associated with worse prognosis in patients with ESCC. miR‑216a‑5p negatively regulated KIAA0101 expression by directly targeting the 3'‑untranslated region of the KIAA0101 mRNA. Overexpression of miR‑216a‑5p suppressed the proliferation, migration, and invasion of the ESCC cell lines, whereas inhibition of miR‑216a‑5p had the opposite effects. Meanwhile, KIAA0101 promoted ESCC migration and invasion, and its overexpression abolished the antitumor effects of miR‑216a‑5p mimics. As a tumor suppressor, miR‑216a‑5p targets KIAA0101 to inhibit the proliferation, migration, and invasion of ESCC. Therefore, the miR‑216a‑5p/KIAA0101 axis may be a potential target for ESCC treatment.
KIAA0101 蛋白(也称为 NS5ATP9 或 Paf15)在食管鳞状细胞癌(ESCC)中过表达,与疾病进展和患者预后不良相关,但 KIAA0101 表达如何受到调节尚不清楚。通过生存分析揭示了肿瘤 miR-216a-5p 表达与 ESCC 患者预后之间的关系。采用定量逆转录酶 PCR 和 Western blot 分析评估人 ESCC 组织和细胞系中 miR-216a-5p 和 KIAA0101 的表达。通过双荧光素酶报告基因检测验证 miR-216a-5p 对 KIAA0101 的靶向作用。将 miR-216a-5p 模拟物和抑制剂转染至 EC9706 和 TE1 细胞系,或转染 KIAA0101 特异性 shRNA 和 KIAA0101 表达质粒,以评估操纵 miR-216a-5p 和 KIAA0101 表达对 ESCC 细胞增殖、细胞周期进展、迁移和侵袭的影响。miR-216a-5p 在 ESCC 组织和细胞系中表达较低,与 KIAA0101 蛋白表达呈负相关。ESCC 患者中 miR-216a-5p 表达较低与预后较差相关。miR-216a-5p 通过直接靶向 KIAA0101 mRNA 的 3'-非翻译区负调控 KIAA0101 表达。过表达 miR-216a-5p 抑制 ESCC 细胞系的增殖、迁移和侵袭,而抑制 miR-216a-5p 则产生相反的效果。同时,KIAA0101 促进 ESCC 迁移和侵袭,而过表达 miR-216a-5p 模拟物则消除其抗肿瘤作用。作为一种肿瘤抑制因子,miR-216a-5p 通过靶向 KIAA0101 抑制 ESCC 的增殖、迁移和侵袭。因此,miR-216a-5p/KIAA0101 轴可能是 ESCC 治疗的潜在靶点。