MiR-942-5p inhibits tumor migration and invasion through targeting CST1 in esophageal squamous cell carcinoma

Abstract

Introduction Cysteine Protease Inhibitor 1 (CST1), a cystatin superfamily protein with the effect on the inhibition of cysteine protease activity, is reported to be involved in the development of many malignancies. MiR-942-5p has been demonstrated its regulatory effects on some malignancies. However, the roles of CST1 and miR-942-5p on esophageal squamous cell carcinoma (ESCC) are still unknown up to now. Methods The expression of CST1 in ESCC tissues was analyzed by TCGA database, immunohistochemistry, and RT-qPCR, respectively. Matrigel-uncoated or-coated transwell assay was used to determine the effect of CST1 on migration and invasion of ESCC cells. Regulatory effect of miR-942-5p on CST1 was detected by dual luciferase assay. Results CST1 was ectopically highly expressed in ESCC tissues, and had the effect on promoting the migration and invasion of ESCC cells by upregulating phosphorylated levels of key effectors including MEK1/2, ERK1/2, and CREB in MEK/ERK/CREB pathway. Dual-luciferase assay results showed that miR-942-5p had a regulatory effect on targeting CST1. Conclusions CST1 plays a carcinogenic role on ESCC, and miR-942-5p can regulate the migration and invasion of ESCC cells by targeting CST1 to downregulate MEK/ERK/CREB signaling pathway, suggesting that miR-942-5p/CST1 axis might be a promising target for diagnosis and treatment of ESCC.

CST1 promotes the metastasis by mediating an oxidative phosphorylation/MEK/ERK axis in esophageal squamous carcinoma cancer

“…Besides, CST1 was found to promote gastric cancer by mediating Wnt/β-catenin/TCF signaling as a downstream effector of transcription factor TCF [33] . Encouringly, CST1 has also been shown its oncogenic potential on ESCC development by our pilot study, manifested as the aberrantly high expression and effect of CST1 on cell migration and invasion by the MEK/ERK signaling pathway in ESCC [30] . Therefore, we further made a comprehensive survey for the potential mechanism of CST1 on ESCC development by performing the transcriptome sequencing for ESCC cell with CST1 knockdown, and surprisingly discovered that the differential genes were closely related to the regulation of cell metabolic processes and mitochondrial respiratory chain-related oxidoreductase activity, and signi cantly enriched in metabolic and tumor-related signaling pathways, suggesting that CST1 might be involved in mediating mitochondrial OXPHOS of ESCC cells.…”

“…Considering the effect of CST1 on the migration and invasion of ESCC cells observed in our pilot study [30] , we made a comprehensive survey for the potential mechanism of CST1 on ESCC development by performing the transcriptome sequencing for ESCC cell line KYSE150 with CST1 knockdown by DESep2 software (Fig 1A). As a result, a total of 2452 differential genes were obtained, including 1181 genes increased and 1271 genes decreased (Fig 1B ); by Gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, the differential genes were shown to be closely related to the regulation of cellular metabolic processes and mitochondrial respiratory chain-related oxidoreductase activity, and signi cantly enriched in metabolic and tumorrelated signaling pathways (Fig 1C, D), suggesting that CST1 might be involved in regulating mitochondrial OXPHOS of ESCC cells.…”

“…Aberrant CST1 expression has been reported to be associated with the development of some malignancies, such as breast, lung, liver and gastric cancers [24][25][26][27][28] . Encouringly, our pilot study has uncovered the aberrantly high expression of CST1 in both serum and cancerous tissues of ESCC patients [29] , and the effect of miR-942-5p/CST1 axis on the migration and invasion of ESCC cells by the MEK/ERK signaling pathway [30] .…”

Validation of serum cystatin SN detection for diagnosis and poor prognosis of esophageal squamous cell carcinoma

“…We suspect that the lack of repeat sequencing and the small sample size are possible reasons. However, after conducting a thorough search of online databases and reviewing multiple studies, it was determined that CST1 may serve as a reliable indicator for early diagnosis and prognosis of ESCC ( 13 , 24 – 26 ). We have tried several commercial ELISA kits, performing not as expected.…”

Inhibition of miR-214 expression by small molecules alleviates head and neck cancer metastasis by targeting ALCAM/TFAP2 signaling

“…The miRs are small non-coding RNAs that regulate multiple gene expressions and control cellular processes, including cell cycle, migration, invasion, and extravasation. Recent studies have reported that miRs play an important role in HNSCC disease development and progression [36][37][38][39]. The therapeutic measures that can edit miRs' function have been recognized as an exciting new area of drug development.…”