Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China.
Cell Death Dis. 2020 Nov 22;11(11):1002. doi: 10.1038/s41419-020-03170-w.
Numerous studies have reported the association of long non-coding RNAs (lncRNAs) in cancers, yet the function of lncRNA high expressed in hepatocellular carcinoma (HEIH) in esophageal carcinoma (EC) has seldom been explored. Here, we aimed to explore the mechanism of HEIH on EC via microRNA-185 (miR-185)/kallikrein-related peptidase 5 (KLK5) modulation. Cancer and non-tumoral tissues were collected, in which HEIH, miR-185 and KLK5 expression were detected, as well as their correlations. Also, the relation between the prognosis of EC patients and HEIH/miR-185/KLK5 expression was clarified. EC cells (KYSE-30 and TE-1) were screened for subsequent gain- and loss-of-function assays and their biological functions were further monitored. Tumor volume and weight in EC mice were also measured. Results from this study indicated that HEIH and KLK5 were elevated and miR-185 was declined in EC. The positive correlation was seen in HEIH and KLK5 expression, while the negative correlation was observed in HEIH or KLK5 and miR-185 expression. High HEIH and KLK5 indicated worse prognosis and high miR-185 suggested better prognosis of EC patients. Depleting HEIH or restoring miR-185 suppressed the malignant phenotypes of EC cells, and delayed tumor growth in EC mice. HEIH was found to bind with miR-185 to regulate KLK5 expression. Overexpressing KLK5 alone promoted EC cell progression while up-regulating miR-185 reversed such effects on EC cells. Collectively, we reveal that HEIH depletion dampens EC progression by upregulating miR-185 and downregulating KLK5, which provides novel treatments for EC.
大量研究报道了长非编码 RNA（lncRNA）在癌症中的相关性，但在食管癌（EC）中很少探索高表达 lncRNA 在肝癌（HEIH）中的功能。在这里，我们旨在通过 microRNA-185（miR-185）/激肽释放酶相关肽 5（KLK5）调节来探讨 HEIH 对 EC 的作用机制。收集癌组织和非肿瘤组织，检测 HEIH、miR-185 和 KLK5 的表达，并分析其相关性。同时，还阐明了 EC 患者的预后与 HEIH/miR-185/KLK5 表达之间的关系。筛选 EC 细胞（KYSE-30 和 TE-1）进行随后的增益和功能丧失实验，并进一步监测其生物学功能。还测量了 EC 小鼠的肿瘤体积和重量。本研究结果表明，HEIH 和 KLK5 在 EC 中升高，miR-185 降低。HEIH 和 KLK5 表达呈正相关，而 HEIH 或 KLK5 与 miR-185 表达呈负相关。高 HEIH 和 KLK5 表明 EC 患者预后较差，高 miR-185 表明预后较好。耗尽 HEIH 或恢复 miR-185 抑制 EC 细胞的恶性表型，并延缓 EC 小鼠的肿瘤生长。发现 HEIH 与 miR-185 结合以调节 KLK5 表达。单独过表达 KLK5 促进 EC 细胞进展，而上调 miR-185 则逆转了对 EC 细胞的这种作用。总之，我们揭示了 HEIH 耗竭通过上调 miR-185 和下调 KLK5 来抑制 EC 进展，为 EC 提供了新的治疗方法。
