A novel cuproptosis-related prognostic lncRNA signature and lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) remains the most common subtype of lung malignancy. Cuproptosis is a newly identified cell death which could regulate tumor cell proliferation and progression. Long non-coding RNAs (lncRNAs) are key molecules and potential biomarkers for diagnosing and treating various diseases. However, the effects of cuproptosis-related lncRNAs on LUAD are still unclear. In our study, 7 cuproptosis-related lncRNAs were selected to establish a prognostic model using univariate Cox regression analysis, LASSO algorithm, and multivariate analysis. Furthermore, we evaluated AC008764.2, AL022323.1, ELN-AS1, and LINC00578, which were identified as protective lncRNAs, while AL031667.3, AL606489.1, and MIR31HG were identified as risk lncRNAs. The risk score calculated by the prognostic model proved to be an effective independent factor compared with other clinical features by Cox regression analyses [univariate analysis: hazard ratio (HR) = 1.065, 95% confidence interval (CI) = 1.043–1.087, P < 0.001; multivariate analysis: HR = 1.067, 95% CI = 1.044–1.091, P < 0.001]. In addition, both analyses (ROC and nomogram) were used to corroborate the accuracy and reliability of this signature. The correlation between cuproptosis-related lncRNAs and immune microenvironment was elucidated, where 7 immune cells and 8 immune-correlated pathways were found to be differentially expressed between two risk groups. Furthermore, our results also identified and verified the ceRNA of cuproptosis-related lncRNA MIR31HG/miR-193a-3p/TNFRSF21 regulatory axis using bioinformatics tools. MIR31HG was highly expressed in LUAD specimens and some LUAD cell lines. Inhibition of MIR31HG clearly reduced the proliferation, migration, and invasion of the LUAD cells. MIR31HG showed oncogenic features via sponging miR-193a-3p and tended to positively regulate TNFRSF21 expression. In a word, lncRNA MIR31HG acts as an oncogene in LUAD by targeting miR-193a-3p to modulate TNFRSF21, which may be beneficial to the gene therapy of LUAD.

An efficient five-lncRNA signature for lung adenocarcinoma prognosis, with AL606489.1 showing sexual dimorphism

“…However, in colorectal cancer ( Xu et al, 2019 ), SATB2-AS1 has the effect of inhibiting tumor cell metastasis. Similar to our result, AC026355.1 was reported to be an immune-related gene with tumor suppressor effects by Li et al ( Li et al, 2020 ) In past studies, AL606489.1 has been reported to be associated with autophagy ( Liu et al, 2021 ), ferroptosis ( Guo et al, 2021 ), cuproptosis ( Mo et al, 2022 ) and pyroptosis ( Li et al, 2018 ; Song et al, 2021 ) processes in LUAD tumor cells. LINC 01843 was first shown to be associated with LUAD progression.…”

Cuproptosis-Related lncRNAs Signature Predicts Prognosis and Chemotherapeutic Response of Patients with Lung Adenocarcinoma

“…Our new discovered CuRLsig (AC138965. 37 . Furthermore, our CuRLsigderived risk model signi cantly outperformed all previous-reported models (Li = 0.637, Jin = 0.629, Zeng = 0.679 and CuRLsig-derived score = 0.718 in TCGA set of 3-year) [27][28][29] .…”

Cuproptosis-related lncRNA signature for prognostic prediction in patients with acute myeloid leukemia

“…Several recent studies confirmed that N6-methyadenosine-related lncRNAs predicted AML prognosis and the immune landscape [20][21][22]. Moreover, it is worth mentioning that cuproptosis-related lncRNA signature also showed promising prognosis prediction potential in carcinomas, including hepatocellular carcinoma [23], lung adenocarcinoma [24], colon adenocarcinoma [25], and colorectal cancer [26]. However, whether cuproptosis-related lncRNA signature could be utilized for the prediction of AML prognosis and immune response is largely unknown.…”