Zhou Wei-Zheng, Wang Xiao-Wei, Zhu Ji, Chen Ming-Zhi, Jin Hai
Department of Thoracic Surgery, The First Affiliated Hospital of the Navy Medical University, Shanghai, PR China.
Department of Thoracic and Cardiovascular Surgery, Yixing People's Hospital affiliated to Jiangsu University, Yixing, Jiangsu Province, PR China.
Histol Histopathol. 2023 Feb;38(2):223-232. doi: 10.14670/HH-18-517. Epub 2022 Sep 16.
LncRNA CASC15 has been determined as a novel tumor-related lncRNA in many cancers. However, the in-detail role of CASC15 remains elusive in esophageal squamous cell carcinoma (ESCC). CASC15 expression level was detected in 113 ESCC tissues and paired adjacent normal tissues and in human ESCC cell lines. The effects of CASC15 on ESCC proliferation, migration, and invasion were assessed using CCK-8 and transwell assays. In addition, the potential downstream molecules of CASC15 were searched and confirmed by software algorithms, RT-qPCR, western blot, dual-luciferase reporter, and rescue experiments. CASC15 was upregulated in ESCC tissues and cell lines. CASC15 overexpression was associated with poorer prognosis in ESCC patients. Functionally, CASC15 knockdown inhibited cell proliferation, migration, and invasion of ESCC cells. Mechanistically, it was confirmed that CASC15 acts as competing endogenous RNA for miR-33a-5p to regulate PTGS2 expression. In addition, rescue assay showed that miR-33a-5p knockdown or PTGS2 overexpression abolished the cell proliferation, migration, and invasion inhibition role of CASC15 knockdown. In conclusion, this study indicates that CASC15 was upregulated in ESCC and CASC15 knockdown hindered ESCC progression through targeting the miR-33a-5p/PTGS2 axis. CASC15 might serve as a novel biomarker and therapeutic target for ESCC.
长链非编码RNA CASC15已被确定为多种癌症中一种新的肿瘤相关长链非编码RNA。然而，CASC15在食管鳞状细胞癌（ESCC）中的具体作用仍不清楚。检测了113例ESCC组织及其配对的癌旁正常组织以及人ESCC细胞系中CASC15的表达水平。采用CCK-8和Transwell实验评估CASC15对ESCC增殖、迁移和侵袭的影响。此外，通过软件算法、RT-qPCR、蛋白质免疫印迹、双荧光素酶报告基因及拯救实验寻找并证实了CASC15潜在的下游分子。CASC15在ESCC组织和细胞系中表达上调。CASC15过表达与ESCC患者较差的预后相关。在功能上，敲低CASC15可抑制ESCC细胞的增殖、迁移和侵袭。机制上，证实CASC15作为miR-33a-5p的竞争性内源性RNA来调节PTGS2的表达。此外，拯救实验表明，敲低miR-33a-5p或过表达PTGS2可消除敲低CASC15对细胞增殖、迁移和侵袭的抑制作用。总之，本研究表明CASC15在ESCC中表达上调，敲低CASC15通过靶向miR-33a-5p/PTGS2轴阻碍ESCC进展。CASC15可能作为ESCC的一种新型生物标志物和治疗靶点。
