Department of Oncology, Jiangyin People's Hospital Affiliated to Nantong University, No. 163 Shoushan Rd, Jiangyin, Jiangsu Province, 214400, China.
Department of Pediatrics, Jiangyin People's Hospital Affiliated to Nantong University, No. 163 Shoushan Rd, Jiangyin, Jiangsu Province, 214400, China.
Comb Chem High Throughput Screen. 2024;27(8):1222-1230. doi: 10.2174/1386207326666230901120611.
Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. LncRNA CASC15 has also been found to play a vital role in malignant tumors.
Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of EMT and to clarify the reasons for its up-regulated expression in CRC.
Quantitative real-time PCR was performed to evaluate the expression of CASC15 in CRC. The biology function of CASC15 on CRC was assessed by experiments, including CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal transition (EMT).
We found that CASC15 was remarkably upregulated in CRC and positively correlated with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically, TCF12 activates CASC15 transcription to mediate its up-regulation, which activates EMT and promotes CRC progression.
Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC. CASC15 may be a new molecular marker and target for CRC.
结直肠癌（CRC）是最常见的胃肠道恶性肿瘤之一。长链非编码 RNA CASC15 也被发现在恶性肿瘤中发挥重要作用。
本研究旨在探讨 CASC15 在结直肠癌中的作用及其对 EMT 的调控机制，并阐明其在 CRC 中上调表达的原因。
采用实时定量 PCR 检测 CASC15 在 CRC 中的表达。通过 CCK8、集落形成、Transwell 检测和流式细胞术等实验评估 CASC15 对 CRC 的生物学功能。通过荧光素酶报告基因实验验证 TCF12 和 CASC15 之间的调控关系。采用实时定量 PCR 和 Western blot 分析评估与上皮间质转化（EMT）相关的生物标志物。
我们发现 CASC15 在 CRC 中显著上调，并与无复发生存率较差呈正相关。CASC15 敲低显著抑制 CRC 的增殖和迁移。此外，CASC15 下调介导了 CRC 的细胞凋亡。机制上，TCF12 激活 CASC15 的转录，介导其上调，从而激活 EMT 并促进 CRC 的进展。
本研究确定了 TCF12/CASC15/EMT 作为 CRC 的新调控信号轴。CASC15 可能是 CRC 的一个新的分子标志物和治疗靶点。
