MicroRNA-148a-3p Directly Targets SERPINE1 to Suppress EMT-Mediated Colon Adenocarcinoma Progression

Hu, Biwen; Chen, Zhenwei; Wang, Xiaoguang; Chen, Fei; Song, Zhengwei; Cao, Canhui

doi:10.2147/cmar.s302777

Cited by 9 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we found decreased miR-148a-3p levels in SW480 and SW620 CRC cells compared to their non-tumor counterpart, consistent with previous data reporting miR-148a-3p expression was significantly downregulated in colon adenocarcinoma, thus contributing to elucidating its suppression as a crucial factor in tumor progression and poor survival in CRC [53,54]. We report that miR-148a-3p overexpression induced selective CRC cytotoxicity, triggering caspase-3-dependent apoptotic cell death via Bcl-2 downregulation, in line with evidence showing that miR-148a-3p overexpression reduced the progression of colon adenocarcinoma [55].…”

Section: Discussionsupporting

confidence: 92%

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

Martino,

Balestrieri,

Aragona

et al. 2023

Cancers

View full text Add to dashboard Cite

Ferroptosis, an iron-dependent form of cell death, and dysregulated microRNA (miRNA) expression correlate with colorectal cancer (CRC) development and progression. The tumor suppressor ability of miR-148a-3p has been reported for several cancers. Nevertheless, the role of miR-148a-3p in CRC remains largely undetermined. Here, we aim at investigating the molecular mechanisms and regulatory targets of miR-148a-3p in the CRC cell death mechanism(s). To this end, miR-148a-3p expression was evaluated in SW480 and SW620 cells and normal colon epithelial CCD 841 CoN cells with quantitative real-time polymerase chain reaction (qRT-PCR). Data reported a reduction of miR-148a-3p expression in SW480 and SW620 cells compared to non-tumor cells (p < 0.05). Overexpression of miR-148a selectively inhibited CRC cell viability (p < 0.001), while weakly affecting normal CCD 841 CoN cell survival (p < 0.05). At the cellular level, miR-148a-3p mimics promoted apoptotic cell death via caspase-3 activation (p < 0.001), accumulation of mitochondrial reactive oxygen species (ROS) (p < 0.001), and membrane depolarization (p < 0.001). Moreover, miR-148a-3p overexpression induced lipid peroxidation (p < 0.01), GPX4 downregulation (p < 0.01), and ferroptosis (p < 0.01), as revealed by intracellular and mitochondrial iron accumulation and ACSL4/TFRC/Ferritin modulation. In addition, levels of SLC7A11 mRNA and protein, the cellular targets of miR-148a-3p predicted by bioinformatic tools, were suppressed by miR-148a-3p’s overexpression. On the contrary, the downregulation of miR-148a-3p boosted SLC7A11 gene expression and suppressed ferroptosis. Together, these in vitro findings reveal that miR-148a-3p can function as a tumor suppressor in CRC by targeting SLC7A11 and activating ferroptosis, opening new perspectives for the rationale of therapeutic strategies through targeting the miR-148a-3p/SLC7A11 pathway.

show abstract

Section: Discussionsupporting

confidence: 92%

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

Martino,

Balestrieri,

Aragona

et al. 2023

Cancers

View full text Add to dashboard Cite

show abstract

“…SERPINE1 , a plasminogen activator inhibitor (PAI-1) protein-coding gene, is located in the long arm of chromosome 7 (7q21.3-q22) and encodes the SERPINE1 protein, a member of the serine protease inhibitor (serpin) superfamily, which rapidly inhibits fibrinogenesis and mediates a variety of pathological processes such as inflammation and cancer [ 18 ]. SERPINE1 is highly expressed in a variety of tumor tissues [ 19 ]. This evidence is substantially in line with the results of the present study that SERPINE1 was overexpressed in oral cancer cells and was linked with poor clinical outcomes in patients.…”

Section: Discussionmentioning

confidence: 99%

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Guo

Sun

Chen

et al. 2023

Clin Exp Otorhinolaryngol

View full text Add to dashboard Cite

Background: Nicotine is an ingredient of tobacco, and its exposure increases various cancer risks, including oral cancer. Previous studies have focused on its addictive properties, but its carcinogenic mechanism has rarely been studied. We aimed to explore the key genes in the process of nicotine promoting the occurrence and development of oral cancer through data mining and experimental verification. Methods: This study involved three parts. First, the key genes related to nicotine-related oral cancer were screened out through data mining; second, the expression and clinical significance of the key gene in oral cancer tissues were verified by bioinformatics. Finally, the expression and clinical significance of the key gene in oral cancer were histologically investigated, and the effects of its expression on cell proliferation, invasion, and drug resistance were cytologically assessed.Results: SERPINE1 was identified as the key gene, which was upregulated in nicotine-treated oral cells and may be an independent prognostic factor for oral cancer. SERPINE1 was enriched in various pathways such as TNF and Apelin pathways; and was related to the infiltration of macrophages, CD4+T cells, and CD8+T cells. Overexpression of SERPINE1 was associated with N staging and may be involved in hypoxia, angiogenesis, and metastasis. Knockdown of SERPINE1 in oral cancer cells resulted in weakened cell proliferation and invasion ability and increased sensitivity to Bleomycin and Docetaxel. Conclusion: This study revealed SERPINE1 as the key gene for nicotine-related oral cancer, indicating that SERPINE1 may be a novel prognostic indicator and therapeutic target for oral carcinoma.

show abstract

“…Gastrin-releasing peptide (GRP) may serve as an independent predictor of survival in patients with colon cancer [ 22 ]. SERPINE1 plays an essential role in remodeling the tumor microenvironment and the infiltration of immune cells [ 23 ]; some noncoding RNAs influence the epithelial–mesenchymal transition of colon cancer by regulating SERPINE1 [ 24 – 26 ].…”

Section: Discussionmentioning

confidence: 99%

Novel six-gene prognostic signature based on colon adenocarcinoma immune-related genes

Zhou

Gao

2022

BMC Bioinformatics

View full text Add to dashboard Cite

Background Colon adenocarcinoma (COAD) is one of the most common gastrointestinal tumors worldwide, and immunotherapy is one of the most promising treatments for it. Identifying immune genes involved in the development and maintenance of cancer is key to the use of tumor immunotherapy. This study aimed to determine the prognostic value of immune genes in patients with COAD and to establish an immune-related gene signature. Differentially expressed genes, immune-related genes (DEIGs), and transcription factors (DETFs) were screened using the following databases: Cistrome, The Cancer Genome Atlas (TCGA), the Immunology Database and Analysis Portal, and InnateDB. We constructed a network showing the regulation of DEIGs by DETFs. Using weighted gene co-expression network analysis, we prepared 5 co-expressed gene modules; 6 hub genes (CD1A, CD1B, FGF9, GRP, SERPINE1, and F2RL2) obtained using univariate and multivariate regression analysis were used to construct a risk model. Patients from TCGA database were divided into high- and low-risk groups based on whether their risk score was greater or less than the mean; the public dataset GSE40967, which contains gene expression profiles of 566 colon cancer patients, was used for validation. Results Survival analysis, somatic gene mutations, and tumor-infiltrating immune cells differed significantly between the high- and low-risk groups. Conclusions This immune-related gene signature could play an important role in guiding treatment, making prognoses, and potentially developing future clinical applications.

show abstract

MicroRNA-148a-3p Directly Targets SERPINE1 to Suppress EMT-Mediated Colon Adenocarcinoma Progression

Cited by 9 publications

References 33 publications

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

MiR-148a-3p Promotes Colorectal Cancer Cell Ferroptosis by Targeting SLC7A11

<i>SERPINE1</i> as an Independent Prognostic Marker and Therapeutic Target for Nicotine-Related Oral Carcinoma

Novel six-gene prognostic signature based on colon adenocarcinoma immune-related genes

Contact Info

Product

Resources

About