Bioinformatic Analyses of the Ferroptosis-Related lncRNAs Signature for Ovarian Cancer

Abstract

Both ferroptosis and lncRNAs are significant for ovarian cancer (OC). Whereas, the study of ferroptosis-related lncRNAs (FRLs) still few in ovarian cancer. We first constructed an FRL-signature for patients with OC in the study. A total of 548 FRLs were identified for univariate Cox regression analysis, and 21 FRLs with significant prognosis were identified. The prognostic characteristics of nine FRLs was constructed and validated, showing opposite prognosis in two subgroups based on risk scores. The multivariate Cox regression analysis and nomogram further verified the prognostic value of the risk model. By calculating ferroptosis score through ssGSEA, we found that patients with higher risk scores exhibited higher ferroptosis scores, and high ferroptosis score was a risk factor. There were 40 microenvironment cells with significant differences in the two groups, and the difference of Stromal score between the two groups was statistically significant. Six immune checkpoint genes were expressed at different levels in the two groups. In addition, five m6A regulators (FMR1, HNRNPC, METTL16, METTL3, and METTL5) were higher expressed in the low-risk group. GSEA revealed that the risk model was associated with tumor-related pathways and immune-associated pathway. We compared the sensitivity of chemotherapy drugs between the two risk groups. We also explored the co-expression, ceRNA relation, cis and trans interaction of ferroptosis-related genes and lncRNAs, providing a new idea for the regulatory mechanisms of FRLs. Moreover, the nine FRLs were selected for detecting their expression levels in OC cells and tissues.

METTL16 suppressed the proliferation and cisplatin-chemoresistance of bladder cancer by degrading PMEPA1 mRNA in a m6A manner through autophagy pathway

“…METTL16 was reported to induce initiation or progression in leukemia [31], hepatocellular cancer [29], pancreatic cancer [30], breast cancer [32], gastric cancer [33], cervical cancer [34] and so on [35][36][37]. Zeng et al [30] demonstrated PDAC cells with high METTL16 expression increased sensitivity to PARPi, especially when combined with gemcitabine.…”

“…These observations imply the existence of additional m6A methyltransferase. Recently, METTL16 (methyltransferase-like 16, also known as METT10D), which belongs to the methyltransferase like (METTL) proteins family, is identified as a novel “writer” that could drive methylation independently of the methyltransferase complex, inducing initiation or progression in hepatocellular cancer 29 , pancreatic ductal adenocarcinoma 30 , leukemia 31 , breast cancer 32 , gastric cancer 33 , cervical cancer 34 and so on 35 - 37 . In addition, Zheng et al 38 predicted that METTL16 may be a good prognostic factor for bladder cancer through bioinformatics analysis.…”

RNA epigenetic modifications in ovarian cancer: The changes, chances, and challenges

“…This indicates that the various RNA modification regulators do not function independently, and that the specific relationship between them needs further exploration. In addition, zinc finger CCCH domain‐containing protein 13 (ZC3H13), VIRMA, and methyltransferase‐like 16 (METTL16) are associated with a poor prognosis of OC (Fan et al, 2020; Zheng et al, 2021; Zhu et al, 2022). Compared with METTL3, little is known about these other m 6 A writers.…”

Novel insights into the interplay between m6A modification and programmed cell death in cancer

“…Although several ferroptosis-associated lncRNAs have been analyzed for their correlation with m6A-related genes in terms of immune efficacy 115 , 116 , 117 , few studies have investigated the specific targets or pathways of m6A and ferroptosis in immune therapy. Given that ferroptosis and m6A play critical roles in tumors, further research on m6A-modified ferroptosis in diverse cancers is needed.…”