miRNA-6715-5p Inhibits Cellular Proliferation and Invasion in Colorectal Cancer by Directly Targeting CST4

Abstract

Background. Data on the correlation between CST4 and colorectal cancer (CRC) metastasis are scarce. The aim of this study was to analyze CST4 expression and investigate its biological roles and related microRNA- (miRNA-) mediated regulation in CRC. Methods. The expression of CST4 was examined in cancer tissues and their corresponding adjacent normal tissues from 40 gastric adenocarcinoma patients. The expression level of CST4 in specimens (cancer and normal tissues) was assessed through immunohistochemistry and/or quantitative polymerase chain reaction. miRNAs targeting CST4 in CRC were predicted by bioinformatics software. CST4 was knocked down in HCT116 cells and candidate miRNAs were transfected into HCT116 cells, and the effects of CST4 knockdown and miRNA transfection on cell proliferation and invasion were examined using CCK8, cell colony formation, and Transwell migration assays. Luciferase double-reporter assays were performed to verify the relationship between miRNA and CST4. Results. The expression of CST4 in CRC tissues was significantly higher than that in normal paracancerous tissues, but the results for miRNA-6715-5p were opposite. Regardless of CST4 knockdown or miRNA-6715-5p overexpression, the proliferation and invasion ability of HCT116 cells decreased significantly. Luciferase double-reporter assays showed that the upregulation of miR-6715-5p significantly reduced the luciferase activities of the CST4 3′-UTR plasmid in HCT116 cells. Conclusion. CST4 may be involved in CRC proliferation and metastasis. miRNA-6715-5p directly targets CST4 and negatively regulates its expression.

Recurrent triple-negative breast cancer from cysteine deprivation loses tumorigenicity via downregulation of the CST4 signaling

“…CSTs have also been suggested as a prognostic biomarker for various cancers [57][58][59]. CST4, known as cystatin SA, was also founded highly expressed in gastric and colorectal cancer to promote cell proliferation, invasion, and metastasis [42,60]. The role of CST4 in breast cancer, particularly in TNB [61]C, remains unclear.…”

Type 2 Cystatins and Their Roles in the Regulation of Human Immune Response and Cancer Progression

“…CYS2 may help regulate the TGF-β signaling pathway and promote EMT like CYS1, but the mechanism needs further exploration to be certain [131]. CST4 is upregulated in esophageal, colon, and gastric cancer and is associated with poor prognosis [133][134][135]. The overexpression of CYSS in gastric tumor cells upregulates a protein called ELFN2, which directly inhibits the expression of E-cadherin and promotes EMT, like CYS1 and CYS2 [134].…”

Downregulated miRNA-491-3p accelerates colorectal cancer growth by increasing uMtCK expression

“…MiRNA is a kind of small non-coding RNA transcript consisting of 19–25 bases ( Goldberger et al, 2013 ; Berindan-Neagoe et al., 2014 ; Boissinot et al, 2020 ); it plays key roles in many physiopathological processes, such as energy metabolism, tumorigenesis, and immune response ( Lenart et al, 2020 ; Gangaraju & Lin, 2009 ; Taniguchi, Uchiyama & Akao, 2021 ). Mounting studies have revealed that a lot of miRNAs are dysregulated in CRC ( Shi, Zhou & Zhang, 2021a ; Lan et al, 2021 ; Zhang et al, 2021 ), prostate cancer ( Coarfa et al, 2016 ), and breast cancer ( Lorenzo-Martin et al., 2019 ), etc. MiRNAs post-transcriptionally regulate gene expression by binding to the 3′ untranslated region (3′ UTR) of target mRNAs, making possible to function as oncogenes, tumor suppressors, or drug resistance factors in different cases ( Shi, Zhou & Zhang, 2021a ; Lan et al, 2021 ; Zhang et al, 2021 ; Wang et al, 2021 ).…”

“…Mounting studies have revealed that a lot of miRNAs are dysregulated in CRC ( Shi, Zhou & Zhang, 2021a ; Lan et al, 2021 ; Zhang et al, 2021 ), prostate cancer ( Coarfa et al, 2016 ), and breast cancer ( Lorenzo-Martin et al., 2019 ), etc. MiRNAs post-transcriptionally regulate gene expression by binding to the 3′ untranslated region (3′ UTR) of target mRNAs, making possible to function as oncogenes, tumor suppressors, or drug resistance factors in different cases ( Shi, Zhou & Zhang, 2021a ; Lan et al, 2021 ; Zhang et al, 2021 ; Wang et al, 2021 ). Dysregulated expression of miRNAs is correlated with cancer cell proliferation, migration, and invasion ( Zhang et al, 2021 ; Li et al, 2015 ; Duan et al, 2017 ; Lan et al, 2021 ; Ding et al, 2022 ).…”