Dataset Information

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

ABSTRACT:

Objective

Colon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING).

Methods

Real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the expression of miR-181a-2-3p in colon cancer cell lines and normal intestinal epithelial cells. After overexpression of miR-181a-2-3p in colon cancer cell lines SW480 and HT29, cells were examined by CCK8, Transwell, and flow cytometry assays for alterations in proliferation, migration, apoptosis, and cell cycle. Target genes of miR-181a-2-3p were predicted by bioinformatics and validated by dual luciferase assays. Rescue experiments were performed to explore the role of STING in the effect of miR-181a-2-3p. The effect of miR-181a-2-3p on colon cancer proliferation in vivo was validated by nude mouse tumorigenicity assay.

Results

miR-181a-2-3p was lowly expressed in both colon cancer tissues and cell lines. Overexpression of miR-181a-2-3p led to reduced proliferation and migration, increased apoptosis, and altered cell cycle in colon cancer cell lines SW480 and HT29. STING was a target gene of miR-181a-2-3p. Increased STING expression partially counteracted the effect of overexpression of miR-181a-2-3p on colon cancer cell lines. miR-181a-2-3p also suppressed colon cancer proliferation in vivo.

Conclusion

miR-181a-2-3p inhibits the proliferation and oncogenicity of colon cancer, and its molecular mechanism could be inhibited by STING.

SUBMITTER: Liu B

PROVIDER: S-EPMC11346793 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

Liu Bowei B Lu Kai K Yuan Lijie L Li Xiaofang X Lan Ling L Han Shuangyin S

Aging 20240809 15

<h4>Objective</h4>Colon cancer is a common malignant tumor of the gastrointestinal system, which is characterized by high morbidity and mortality. The purpose of this study was to analyze the expression and biological role of miR-181a-2-3p in colon cancer and to investigate the molecular mechanism of its regulatory effect on colon cancer through stimulator of interferon genes (STING).<h4>Methods</h4>Real-time reverse transcription polymerase chain reaction (qRT-PCR) assay was used to detect the ...[more]

PMID: 39133165

Similar Datasets

Project description:This study aimed to determine the effect of miR-186-3p and KRT18 interaction on the biological behavior of colon cancer cells. A biotin-microRNA pull-down assay was performed to identify potential miRNAs. qRT-PCR was used to verify the KRT18 and miR-186-3p levels. In addition, Western blotting was used to detect the KRT18 protein levels. The functional connection between KRT18 and miR-186-3p was confirmed using a dual luciferase reporter assay. BrdU incorporation, MTT assay, and flow cytometry were performed to verify the biological function coupled with in vivo assays. A significant decrease in miR-186-3p expression was observed in colon carcinoma tissues and cells. Functionally, overexpression of miR-186-3p displayed an obvious suppressive action on cell proliferation and viability, and a stimulatory action on the apoptotic ability of SW620 and SW480 cells. Conversely, reduced miR-186-3p had a marked stimulatory effect on proliferation and viability, and a suppressive apoptotic effect. Inhibition of tumorigenesis was observed in mice treated with the miR-186-3p agomir. Furthermore, we identified that miR-186-3p regulated KRT18 levels in colon carcinoma, where silenced KRT18 suppressed proliferation and viability and promoted apoptosis. However, the addition of a miR-186-3p inhibitor weakened the effects of si-KRT18. Additionally, the activation of MAPK signaling pathway upon miR-186-3p silencing was antagonized by the combined transfection of si-KRT18 and miR-186-3p inhibitor. miR-186-3p suppresses proliferation and viability, but facilitates apoptosis in colon cancer cells by targeting KRT18 and negatively regulating the MAPK signaling pathway, indicating that the miR-186-3p/KRT18 axis may be a promising therapeutic target for colon carcinoma.Abbreviations: KRT18: keratin 18; NC: negative control; si‑: small interfering RNA; inhibitor: miR-186-3p inhibitor; OD: optical density; PI: propidium iodide; FITC: fluorescein isothiocyanate; 3'UTR: 3'untranslated region; WT: wild-type; MUT: mutant-type; miR: microRNA.

Project description:The aim of the present study was to identify the differentially expressed microRNAs (DEMs) between Lynch syndrome (LS) and the normal colonic (N-C) control samples, predict the target genes (TGs) and analyze the potential functions of the DEMs and TGs. The miRNA expression dataset GSE30454, which included data of 13 LS and 20 N-C tissue samples, was downloaded from the Gene Expression Omnibus. The classical t-test in Linear Models for Microarray Data package was used for DEM identification. TG prediction was performed using 5 databases. The regulatory network of the DEMs and their TGs was constructed using Cytoscape. Functional and pathway enrichment analysis was performed. The transcription factors (TFs), tumor-associated genes (TAG) and tumor suppressor genes (TSGs) were then identified. Three key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p were identified. Hsa-miR-520e and hsa-miR-137 had 4 common TGs, including SNF related kinase, metal-regulatory transcription factor 1 (MTF1), round spermatid basic protein 1 and YTH N6-methyladenosine RNA binding protein 3; hsa-miR-590-3p and hsa-miR-137 had 14 common TGs, including NCK adaptor protein 1 (NCK1), EPH receptor A7, and stress-associated endoplasmic reticulum protein 1; hsa-miR-590-3p and hsa-miR-520e had 12 common TGs, including Krüppel-like factor (KLF) 13, twinfilin actin binding protein 1, and nuclear factor I B. Through the functional and pathway enrichments analysis, MTF1 was involved in regulation of gene expression and metabolic processes, and sequence-specific DNA binding TF activity. KLF13 was involved in regulation of gene expression and regulation of cellular metabolic processes. NCK1 was enriched in the axon guidance pathway. In addition, the functional and pathway enrichment analysis showed certain TGs, such as hypoxia-inducible factor 1α, AKT serine/threonine kinase 2, and rapamycin-insensitive companion of mammalian target of rapamycin, participated in the mTOR signaling pathway. The 3 key DEMs hsa-miR-137, hsa-miR-520e, and hsa-miR-590-3p may have important roles in the process of LS.

Project description:BackgroundGastric cancer (GC) is the fifth most commonly diagnosed cancer worldwide. Due to the dismal prognosis, identifying novel therapeutic targets in GC is urgently needed. Evidences have shown that miRNAs played critical roles in the regulation of tumor initiation and progression. GLI family zinc finger 2 (GLI2) has been reported to be up-regulated and facilitate cancer progression in multiple malignancies. In this study, we focused on identifying GLI2-targeted miRNAs and clarifying the underlying mechanism in GC.MethodsPaired fresh gastric cancer tissues were collected from gastrectomy patients. GLI2 and miRNAs expression were detected in gastric cancer tissues and cell lines. Bioinformatics analysis was used to predict GLI2-targeted miRNAs and dual-luciferase reporter assay was applied for target verification. CCK-8, clone formation, transwell and flow cytometry were carried out to determine the proliferation, migration, invasion and cell cycle of gastric cancer cells. Tumorsphere formation assay and flow cytometry were performed to detail the stemness of gastric cancer stem cells (GCSCs). Xenograft models in nude mice were established to investigate the role of the miR-144-3p in vivo.ResultsGLI2 was frequently upregulated in GC and indicated a poor survival. Meanwhile, miR-144-3p was downregulated and negatively correlated with GLI2 in GC. GLI2 was a direct target gene of miR-144-3p. MiR-144-3p overexpression inhibited proliferation, migration and invasion of gastric cancer cells. Enhanced miR-144-3p expression inhibited tumorsphere formation and CD44 expression of GCSCs. Restoration of GLI2 expression partly reversed the suppressive effect of miR-144-3p. Xenograft assay showed that miR-144-3p could inhibit the tumorigenesis of GC in vivo.ConclusionsMiR-144-3p was downregulated and served as an essential tumor suppressor in GC. Mechanistically, miR-144-3p inhibited gastric cancer progression and stemness by, at least in part, regulating GLI2 expression.

Dataset Information

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

Objective

Methods

Results

Conclusion

Publications

Hsa-miR-181a-2-3p inhibits the oncogenicity of colon cancer by directly targeting STING.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets