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.

Expression And Prognostic Role of PRDX1 In Gastrointestinal Cancers

“…These observations suggest a possible oncogenic role of PRDX1 in ESCC. Wu et al 43 reported that miR-375, by directly targeting PRDX1 mRNA, reduces PRDX1 expression levels, thereby inhibiting the proliferation and migration of ESCC cells. A study by Chen et al 42 identified PRDX1 as a regulatory factor influencing the formation of primary cilia in ESCC cells.…”

Prognostic potential of miR-144 in various cancers: A meta-analysis

“…[ 25 ] In laryngeal squamous cell carcinoma (LSCC), Wu et al observed that miR-144 functioned as a tumor suppressor via targeting IRS1. [ 27 ] In addition, related studies have further confirmed that the expression of miR-144 is positively correlated with the expression of apoptosis-related genes such as TP53, FASL, CASP3 and so on. [ 28 ] Related studies have further confirmed that the overexpression of miR-144 is related to the mechanism of vascular endothelial injury caused by atherosclerosis, which involves the 7-KC-MiR-144-IDH2 signal pathway.…”

MicroRNA-375 promotes migration and invasion of Helicobacter pylori-induced gastric cancer cells in vitro

“…miR-375 may play different roles in different cancers. The overexpressed miR-375 can suppress the growth of esophageal squamous cell tumors, and the downregulation of miR-375 can promote the malignant lesions of oral squamous cell carcinoma (23)(24)(25).…”