<scp>TIMP1</scp> promotes cell proliferation and invasion capability of right‐sided colon cancers via the <scp>FAK</scp>/Akt signaling pathway

Ma, Beiyue; Ueda, Hiroyuki; Okamoto, Koichi; Bando, Masahiro; Fujimoto, Shota; Okada, Yasuyuki; Kawaguchi, Tomoyuki; Wada, Hironori; Miyamoto, Hiroshi; Shimada, Mitsuo; Sato, Yasushi; Takayama, Tetsuji

doi:10.1111/cas.15567

Cited by 21 publications

(14 citation statements)

References 42 publications

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“…However, further study is required since no increase in MUC1 expression has been reported in animal trials. TIMP1 has been identified as a key contender in colorectal cancer promotion associated with UC (45). TIMP1, an inducible form, is a member of a four-member glycoprotein family that mediates extracellular matrix turnover (46).…”

Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Qian¹,

Tang²,

Ouyang³

et al. 2023

Ann Transl Med

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Background: Ulcerative colitis (UC) is an idiopathic, chronic disorder characterized by inflammation, injury, and disruption of the colonic mucosa. However, there are still many difficulties in the diagnosis and differential diagnosis of UC. An increasing amount of research has shown a connection between ferroptosis and the etiology of UC. Therefore, our study aimed to identify the key genes related to ferroptosis in UC to provide new ideas for diagnosis UC.Methods: Gene expression profiles of normal and UC samples were extracted from the Gene Expression Omnibus (GEO) database. By combining differentially expressed genes (DEGs), Weighted correlation network analysis (WGCNA) genes, and ferroptosis-related genes, hub genes were identified and then screened using Lasso regression. Based on the key genes, gene ontology (GO) and gene set enrichment analysis (GSEA) analyses were performed. We used NaiveBeyas, Logistic, IBk, and RandomForest algorithms to build a disease diagnosis model using the hub genes. The model was validated using GSE87473 as the validation set.Results: Gene expression matrices of GSE87466 and GSE75214 were downloaded from the GEO database, including 184 UC patients and 43 control samples. A total of 699 DEGs were obtained. From FerrDb, 565 genes related to ferroptosis were identified. The 1,513 genes with the highest absolute correlation coefficient value in the MEblue module were obtained from WGCNA analysis. Five hub genes (LCN2, MUC1, PARP8, PLIN2, and TIMP1) were identified using the Lasso regression algorithm based on the overlapped DEGs, WGCNA-identified genes, and ferroptosis-related genes. GO and GSEA analyses revealed that 5 hub genes were identified as being involved in the negative regulation of transcription by competitive promoter binding, cellular response to citrate cycle_tca_cycle, cytosolic_dna_sensing pathway, UV-A, and beta-alanine metabolism. The logistic algorithm's values of the area under the curve (AUC)were 1.000 and 0.995 for training and validation cohorts, and sensitivity is 0.962, specificity is 1.000, respectively, as determined by comparing various methods. Conclusions:The previously described hub genes were identified as being intimately related to ferroptosis in UC and capable of distinguishing UC patients from controls. By detecting the expression of several genes, this model may aid in diagnosing UC and understanding the etiology and treatment of the disease.

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Section: Discussionmentioning

confidence: 99%

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Qian¹,

Tang²,

Ouyang³

et al. 2023

Ann Transl Med

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“…It should be noted that the effective usage of Timp1-targeted constructions, such as siRNA and shRNA, for the treatment of liver fibrosis [ 104 , 118 ] and other diseases accompanied by an imbalance in the synthesis/degradation of ECM components, such as keloids, was shown [ 119 ]. Additionally, Timp1 knockdown decreases proliferation, migration and invasion of tumor cells of diverse origins [ 120 , 121 , 122 ].…”

Section: Discussionmentioning

confidence: 99%

siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

Chernikov

Staroseletz

Татарникова

et al. 2023

IJMS

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Acute lung injury is a complex cascade process that develops in response to various damaging factors, which can lead to acute respiratory distress syndrome. Within this study, based on bioinformatics reanalysis of available full-transcriptome data of acute lung injury induced in mice and humans by various factors, we selected a set of genes that could serve as good targets for suppressing inflammation in the lung tissue, evaluated their expression in the cells of different origins during LPS-induced inflammation, and chose the tissue inhibitor of metalloproteinase Timp1 as a promising target for suppressing inflammation. We designed an effective chemically modified anti-TIMP1 siRNA and showed that Timp1 silencing correlates with a decrease in the pro-inflammatory cytokine IL6 secretion in cultured macrophage cells and reduces the severity of LPS-induced acute lung injury in a mouse model.

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“…TIMP1 belongs to the TIMP gene family, and encodes a natural inhibitor of MMP. It has been demonstrated that TIMP1 promotes the development of pancreatic cancer, CRC, lung cancer, and gastric cancer (24)(25)(26)(27). It has been reported that overexpression of TIMP1 is associated with poor prognosis and activates the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway to promote the proliferation and invasiveness of CRC cells (25,28).…”

Section: Discussionmentioning

confidence: 99%

“…It has been demonstrated that TIMP1 promotes the development of pancreatic cancer, CRC, lung cancer, and gastric cancer (24)(25)(26)(27). It has been reported that overexpression of TIMP1 is associated with poor prognosis and activates the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway to promote the proliferation and invasiveness of CRC cells (25,28). MMP10 belongs to the MMP family, and is a key target of the protein kinase C iota/partitioning defective protein-6 alpha/ras-related C3 botulinum toxin substrate 1 (PKCι/Par6α/Rac1) axis.…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Model based on a Coagulation-related Gene Signature for Colorectal Cancer

Tang

Zhang

et al. 2023

Preprint

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Background Colorectal cancer (CRC) is a relatively common malignancy worldwide. The diagnosis of CRC at an early stage is difficult due to the lack of effective molecular biomarkers. Consequently, CRC is associated with a high mortality rate. Researchers have shown that coagulation-related factors promote or inhibit CRC progression. The purpose of this study was to identify coagulation-related genes (CRGs) with prognostic value that can potentially serve as therapeutic targets for CRC.Methods In this study, we used data of CRC samples from The Cancer Genome Atlas to identify differentially expressed CRGs. Next, the prognostic model was constructed using Cox proportional hazards regression analysis. The accuracy of the model and survival rate of patients with CRC were analyzed using receiver operating characteristic and Kaplan–Meier curves, respectively. In addition, a nomogram was developed to provide clinical guidance. Subsequently, the model was verified using data from the Gene Expression Omnibus. We evaluated the efficacy of immunotherapy and drug sensitivity using the Tumor Immune Dysfunction and Exclusion algorithms and the Genomics of Drug Sensitivity in Cancer, respectively. The expression of inhibin subunit beta B (INHBB) was knocked down using specific siRNA, and the oncogenic effect of INHBB in colon cancer cells was investigated in vitro.Results We identified seven prognostic CRGs, and constructed a model using five of those (TIMP1, MMP10, WDR72, INHBB, F2RL2). We used the median value to divide patients with CRC into high- and low-risk groups. In The Cancer Genome Atlas cohort, the survival time of patients in the latter group was longer, and the receiver operating characteristic area under curve was ≥ 0.6. The nomogram was successfully constructed. The results of the drug sensitivity analysis suggested that cisplatin, camptothecin, foretinib, tamoxifen, and vinblastine were more effective in the high-risk group versus the low-risk group; the inverse was observed for immunotherapy. Finally, knockdown of INHBB attenuated the proliferation, invasion, and migration of CRC cells in vitro.Conclusion We identified a novel CRG marker in CRC, which may be used as a predictive biomarker and lay the foundation for the personalized treatment of patients with CRC.

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TIMP1 promotes cell proliferation and invasion capability of right‐sided colon cancers via the FAK/Akt signaling pathway

Cited by 21 publications

References 42 publications

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

Identification of ferroptosis-related genes in ulcerative colitis: a diagnostic model with machine learning

siRNA-Mediated Timp1 Silencing Inhibited the Inflammatory Phenotype during Acute Lung Injury

A Novel Prognostic Model based on a Coagulation-related Gene Signature for Colorectal Cancer

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