Dataset Information

Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma.

ABSTRACT: Ferroptosis is a form of programmed cell death that participates in diverse physiological processes. Increasing evidence suggests that long noncoding RNAs (lncRNAs) regulate ferroptosis in tumors, including stomach adenocarcinoma (STAD). In the present study, RNA‑sequencing data from The Cancer Genome Atlas database and ferroptosis‑related markers from the FerrDb data resource were analyzed to select differentially expressed lncRNAs. Univariate and multivariate Cox regression analyses were performed on these differentially expressed lncRNAs to screen 12 lncRNAs linked with overall survival (OS) and 13 associated with progression‑free survival (PFS). Subsequently, two signatures for predicting OS and PFS were established based on these lncRNAs. Kaplan‑Meier analyses indicated that the high‑risk group of patients with STAD had relatively poor prognosis. The areas under the receiver operating characteristic curves of the two signatures indicated their excellent efficacy in predicting STAD prognosis. In addition, the effect of the lncRNA LASTR on proliferation and migration in gastric cancer was confirmed and the relationship between LASTR and ferroptosis was initially explored through experiments. These results provide potential novel targets for tumor treatment and promote personalized medicine.

SUBMITTER: Wang G

PROVIDER: S-EPMC8855154 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma.

Wang Gongjun G Sun Libin L Wang Shasha S Guo Jing J Xiao Ruoxi R Li Wenqian W Qi Weiwei W Qiu Wensheng W

Molecular medicine reports 20220209 4

Ferroptosis is a form of programmed cell death that participates in diverse physiological processes. Increasing evidence suggests that long noncoding RNAs (lncRNAs) regulate ferroptosis in tumors, including stomach adenocarcinoma (STAD). In the present study, RNA‑sequencing data from The Cancer Genome Atlas database and ferroptosis‑related markers from the FerrDb data resource were analyzed to select differentially expressed lncRNAs. Univariate and multivariate Cox regression analyses were perfo ...[more]

PMID: 35137922

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Project description:Background: Ferroptosis is a form of regulated cell death that follows cell membrane damage and mostly depends on iron-mediated oxidative. Long non-coding RNAs (LncRNAs) are associated with the development of a variety of tumors. Till date, LncRNAs have been reported to intervene in ferroptosis. Therefore, we intended to provide a prognostic ferroptosis-related-lncRNA signature in stomach adenocarcinoma (STAD). Methods: We downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. Gene differential expression analysis was performed using the "limma" package. We used Cox regression analysis to determine the ferroptosis-related lncRNAs signature with the lowest AIC value. The Kaplan-Meier curve, ROC curve, and nomogram were used to evaluate the prognostic value of the risk score. Gene set enrichment analysis (GSEA) was used to explore the biologic functions of the three ferroptosis-related lncRNAs. LINC01615 expression in gastric cancer cell lines and tissues was measured by real-time PCR. A nuclear-cytoplasmic fractionation assay was used to analyze the subcellular localization for LINC01615. Furthermore, we used bioinformatics to predict potential target microRNAs (miRNAs) of LINC01615 and their target ferroptosis-related mRNAs. Results: Three ferroptosis-related-lncRNA signatures (AP000695.2, AL365181.3, and LINC01615) were identified, and then Kaplan-Meier, Cox regression analyses, and ROC curve confirmed that the ferroptosis-related-lncRNA model could predict the prognosis of STAD. The GSEA indicated that the three ferroptosis-related lncRNAs might be related to the extracellular matrix and cellular activities. LINC01615 is highly expressed in gastric cancer cell lines and tissues. A nuclear-cytoplasmic fractionation assay confirmed that in gastric cancer cell lines, most LINC01615 was enriched in the cytoplasm. Bioinformatics further predicts four potential target miRNAs of LINC01615 and then figured out 26 target ferroptosis-related mRNAs. Conclusion: We established a three-ferroptosis-related-lncRNA model (AP000695.2, AL365181.3, and LINC01615) that can predict the prognosis of STAD patients. We also expected to provide a promising target for LINC01615 for research in the future, which was highly expressed in gastric cancer and cell lines and acted as a ceRNA to get involved in ferroptosis.

Project description:Background: Long non-coding RNAs (lncRNAs) are key regulators of pancreatic cancer development and are involved in ferroptosis regulation. LncRNA transcript levels serve as a prognostic factor for pancreatic cancer. Therefore, identifying ferroptosis-related lncRNAs (FRLs) with prognostic value in pancreatic cancer is critical. Methods: In this study, FRLs were identified by combining The Cancer Genome Atlas (TCGA) and FerrDb databases. For training cohort, univariate Cox, Lasso, and multivariate Cox regression analyses were applied to identify prognosis FRLs and then construct a prognostic FRLs signature. Testing cohort and entire cohort were applied to validate the prognostic signature. Moreover, the nomogram was performed to predict prognosis at different clinicopathological stages and risk scores. A co-expression network with 76 lncRNA-mRNA targets was constructed. Results: Univariate Cox analysis was performed to analyze the prognostic value of 193 lncRNAs. Furthermore, the least absolute shrinkage and selection operator and the multivariate Cox analysis were used to assess the prognostic value of these ferroptosis-related lncRNAs. A prognostic risk model, of six lncRNAs, including LINC01705, AC068620.2, TRAF3IP2-AS1, AC092171.2, AC099850.3, and MIR193BHG was constructed. The Kaplan Meier (KM) and time-related receiver operating characteristic (ROC) curve analysis were performed to calculate overall survival and compare high- and low-risk groups. There was also a significant difference in survival time between the high-risk and low-risk groups for the testing cohort and the entire cohort, with AUCs of .723, .753, respectively. Combined with clinicopathological characteristics, the risk model was validated as a new independent prognostic factor for pancreatic adenocarcinoma through univariate and multivariate Cox regression. Moreover, a nomogram showed good prediction. Conclusion: The signature of six FRLs had significant prognostic value for pancreatic adenocarcinoma. They may be a promising therapeutic target in clinical practice.

Dataset Information

Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma.

Publications

Ferroptosis‑related long non‑coding RNAs and the roles of LASTR in stomach adenocarcinoma.

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