Wu Kunpeng, Liu Feng, Zhang Tingting, Zhou Zhiliang, Yu Shouqiang, Quan Yonghui, Zhu Shaojin
Department of Thoracic Surgery, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China.
Department of Gastroenterology, Nanjing Lishui People's Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China.
J Gastrointest Oncol. 2022 Oct;13(5):2154-2168. doi: 10.21037/jgo-22-929.
Esophageal cancer (EC) is one of the most lethal cancers. Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype in Asian people. Diverse microRNAs, such as miR-375, have been confirmed to be involved in the process of tumorigenesis and metastasis. However, the underlying mechanism through which miR-375 acts in ESCC patients remains unknown.
We used The Cancer Genome Atlas (TCGA) database to analyze the association between miR-375 and the survival rate in patients with esophageal squamous cell carcinoma. Real Time quantitative PCR (RT-qPCR) analysis was performed to evaluate the level of miR-375 in EC tissues and cells. A luciferase reporter assay was used to confirm the target gene of miR-375. A colony formation assay as well as flow cytometric and transwell invasion experiments were employed to examine the effects of miR-375 and on ESCC cells. A tumor xenograft mouse model was then used to investigate the role of miR-375 on tumor growth . Moreover, we performed rescue experiments to evaluate the effect of on ESCC progression.
miR-375 expression was significantly downregulated in both ESCC clinical tissues and serum, and the reduction of miR-375 was remarkably linked to a poor prognosis in ESCC. Further investigation illustrated that aberrant expression of miR-375 dampened the growth and infiltration of ESCC cells both and . Bioinformatics and luciferase reporter analysis verified that the transcript of is a direct target of miR-375 and its expression in ESCC cells was found to be inversely modulated by miR-375. Moreover, the tumor formation experiment in nude mice confirmed that miR-375 can effectively dampen tumor growth in xenograft tumor mice models. Notably, over-expression of PRDX1 effectively counteracted the tumor-suppressing capabilities of miR-375.
We demonstrated the antitumor effect of miR-375 on ESCC by targeting both and .
食管癌（EC）是最致命的癌症之一。食管鳞状细胞癌（ESCC）是亚洲人群中最常见的组织学亚型。多种微小RNA，如miR-375，已被证实参与肿瘤发生和转移过程。然而，miR-375在ESCC患者中发挥作用的潜在机制仍不清楚。
我们使用癌症基因组图谱（TCGA）数据库分析miR-375与食管鳞状细胞癌患者生存率之间的关联。进行实时定量PCR（RT-qPCR）分析以评估EC组织和细胞中miR-375的水平。使用荧光素酶报告基因测定法来确认miR-375的靶基因。采用集落形成测定法以及流式细胞术和Transwell侵袭实验来检测miR-375对ESCC细胞的影响。然后使用肿瘤异种移植小鼠模型来研究miR-375对肿瘤生长的作用。此外，我们进行了挽救实验以评估其对ESCC进展的影响。
miR-375在ESCC临床组织和血清中的表达均显著下调，miR-375的降低与ESCC的不良预后显著相关。进一步研究表明，miR-375的异常表达抑制了ESCC细胞在体内和体外的生长和浸润。生物信息学和荧光素酶报告基因分析证实，PRDX1的转录本是miR-375的直接靶标，并且发现其在ESCC细胞中的表达受到miR-375的反向调节。此外，裸鼠肿瘤形成实验证实，miR-375可以有效抑制异种移植肿瘤小鼠模型中的肿瘤生长。值得注意的是，PRDX1的过表达有效地抵消了miR-375的肿瘤抑制能力。
我们通过在体内和体外靶向PRDX1证明了miR-375对ESCC的抗肿瘤作用。
