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MiR-375 suppresses the growth and metastasis of esophageal squamous cell carcinoma by targeting PRDX1.


ABSTRACT:

Background

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.

Methods

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 peroxiredoxin 1 (PRDX1) on ESCC cells. A tumor xenograft mouse model was then used to investigate the role of miR-375 on tumor growth in vivo. Moreover, we performed rescue experiments to evaluate the effect of PRDX1 on ESCC progression.

Results

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 in vitro and in vivo. Bioinformatics and luciferase reporter analysis verified that the transcript of PRDX1 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.

Conclusions

We demonstrated the antitumor effect of miR-375 on ESCC by targeting PRDX1 both in vitro and in vivo.

SUBMITTER: Wu K 

PROVIDER: S-EPMC9660039 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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miR-375 suppresses the growth and metastasis of esophageal squamous cell carcinoma by targeting PRDX1.

Wu Kunpeng K   Liu Feng F   Zhang Tingting T   Zhou Zhiliang Z   Yu Shouqiang S   Quan Yonghui Y   Zhu Shaojin S  

Journal of gastrointestinal oncology 20221001 5


<h4>Background</h4>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.<h4>Methods</h4>We used The Cancer Genome Atlas (TCGA) database to analyze the association between miR-375 and  ...[more]

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