Department of Clinical Laboratory, Chinese PLA General Hospital, Beijing 100853, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan, China.
Cancer Biomark. 2018;22(4):787-797. doi: 10.3233/CBM-181354.
Breast cancer is the most common malignancy in women which increases gradually all over the world. LncRNA GACAT3 has been found to be increased in gastric cancer and associated with tumor malignancy. However, whether GACAT3 plays a role in the regulation of breast cancer is not known. In the present study, we found that GACAT3 expression was increased in breast cancer tissues and cells compared with adjacent normal tissues and normal cells. High GACAT3 expression was correlated with the poor prognosis of breast cancer patients. GACAT3 and cyclin D2 (CCND2) contained a binding site of miR-497. miR-497 was decreased in breast cancer tissues and cells compared with adjacent normal tissues and normal cells. Low miR-497 expression was correlated with the poor prognosis of breast cancer patients. In breast cancer tissues, the expression of miR-497 was negatively correlated with GACAT3. Downregulation of GACAT3 increased miR-497 expression. miR-497 mimic reduced the luciferase of GACAT3 and CCND2. Anti-miR-497 reversed the effects of GACAT3 downregulation. We also found that GACAT3 may act as a ceRNA for miR-497, enhancing the expression of CCND2. In conclusion, GACAT3 promotes breast cancer malignancy by sponging miR-497, leading to the enhancement of its endogenous target CCND2. These results suggest that GACAT3/miR-497/CCND2 is a potential therapeutic target and biomarker for breast cancer.
乳腺癌是全世界女性中最常见的恶性肿瘤，其发病率逐渐增加。研究发现，LncRNA GACAT3 在胃癌中表达升高，并与肿瘤恶性程度相关。然而，GACAT3 是否在乳腺癌的调控中发挥作用尚不清楚。本研究发现，与相邻正常组织和正常细胞相比，乳腺癌组织和细胞中的 GACAT3 表达增加。高 GACAT3 表达与乳腺癌患者的预后不良相关。GACAT3 和细胞周期蛋白 D2（CCND2）含有 miR-497 的结合位点。与相邻正常组织和正常细胞相比，乳腺癌组织和细胞中的 miR-497 表达降低。低 miR-497 表达与乳腺癌患者的预后不良相关。在乳腺癌组织中，miR-497 的表达与 GACAT3 呈负相关。下调 GACAT3 增加了 miR-497 的表达。miR-497 模拟物降低了 GACAT3 和 CCND2 的荧光素酶活性。抗 miR-497 逆转了 GACAT3 下调的作用。我们还发现，GACAT3 可能作为 miR-497 的 ceRNA，增强其内源性靶标 CCND2 的表达。综上所述，GACAT3 通过海绵吸附 miR-497 促进乳腺癌恶性进展，从而增强其内源性靶标 CCND2 的表达。这些结果表明，GACAT3/miR-497/CCND2 可能是乳腺癌的潜在治疗靶点和生物标志物。
