Identification of m7G-associated lncRNA prognostic signature for predicting the immune status in cutaneous melanoma.

RNA modifications, including RNA methylation, are widely existed in cutaneous melanoma (CM). Among epigenetic modifications, N7-methylguanosine (m7G) is a kind of modification at 5' cap of RNA which participate in maintaining the stability of mRNA and various cell biological processes. However, there is still no study concerning the relationship between CM and m7G methylation complexes, METTL1 and WDR4. Here, long non-coding RNA (lncRNAs) and gene expression data of CM from the Cancer Genome Atlas (TCGA) database were retrieved to identify differentially expressed m7G-related lncRNAs connected with overall survival of CM. Then, Cox regression analyses was applied to construct a lncRNA risk signature, the prognostic value of identified signature was further evaluated. As a result, 6 m7G-associated lncRNAs that were significantly related to CM prognosis were incorporated into our prognostic signature. The functional analyses indicated that the prognostic model was correlated with patient survival, cancer metastasis, and growth. Meanwhile, its diagnostic accuracy was better than conventional clinicopathological characteristics. The pathway enrichment analysis showed that the risk model was enriched in several immunity-associated pathways. Moreover, the signature model was significantly connected with the immune subtypes, infiltration of immune cells, immune microenvironment, as well as several m6A-related genes and tumor stem cells. Finally, a nomogram based on the calculated risk score was established. Overall, a risk signature based on 6 m7G-associated lncRNAs was generated which presented predictive value for the prognosis of CM patients and can be further used in the development of novel therapeutic strategies for CM.

Exosome miR-23a-3p from Osteoblast Alleviates Spinal Cord Ischemia/Reperfusion Injury by Down-Regulating KLF3-Activated CCNL2 Transcription.

BACKGROUND: Spinal cord ischemia/reperfusion injury (SCIRI) is usually caused by spinal surgery or aortic aneurysm surgery and can eventually lead to paralysis or paraplegia and neurological dysfunction. Exosomes are considered as one of the most promising therapeutic strategies for SCIRI as they can pass the blood-spinal barrier. Previous studies have proved that exosomes secreted by osteocytes have a certain slowing effect on SCIRI. AIM: We aimed to explore the effect of osteoblast secreted exosomes on SCIRI. METHODS: First, neurons and osteoblasts were co-cultured under different conditions. GEO database was utilized to detect the expression of miR-23a-3p in osteoblast exosomes. SCIRI cells were treated with exosomes, and the detection was taken to prove whether miR-23a-3p could slow the progression of SCIRI. Downstream gene and the potential regulatory mechanism were explored through database and functional experiments. RESULTS: MiR-23a-3p was highly expressed in exosomes and it slowed down the process of SCIRI. Downstream mRNA KLF3 could bind to miR-23a-3p and was highly expressed in IRI. Moreover, CCNL2 was regulated by KLF3 and was highly expressed in IRI. Rescue experiments verified that miR-23a-3p suppressed the transcription of CCNL2 by targeting KLF3. CONCLUSION: Exosome miR-23a-3p from osteoblast alleviates SCIRI by down-regulating KLF3-activated CCNL2 transcription.

A novel pyroptosis-associated gene signature for immune status and prognosis of cutaneous melanoma.

BACKGROUND: Cutaneous melanoma (CM) is a life-threatening destructive malignancy. Pyroptosis significantly correlates with programmed tumor cell death and its microenvironment through active host-tumor crosstalk. However, the prognostic value of pyroptosis-associated gene signatures in CM remains unclear. METHODS: Gene profiles and clinical data of patients with CM were downloaded from The Cancer Genome Atlas (TCGA) to identify differentially expressed genes associated with pyroptosis and overall survival (OS). We constructed a prognostic gene signature using LASSO analysis, then applied immune cell infiltration scores and Kaplan-Meier, Cox, and pathway enrichment analyses to determine the roles of the gene signature in CM. A validation cohort was collected from the Gene Expression Omnibus (GEO) database. RESULTS: Four pyroptosis-associated genes were identified and incorporated into a prognostic gene signature. Integrated bioinformatics findings showed that the signature correlated with patient survival and was associated with tumor growth and metastasis. The results of Gene Set Enrichment Analysis of a risk signature indicated that several enriched pathways are associated with cancer and immunity. The risk signature for immune status significantly correlated with tumor stem cells, the immune microenvironment, immune cell infiltration and immune subtypes. The expression of four pyroptosis genes significantly correlated with the OS of patients with CM and was related to the sensitivity of cancer cells to several antitumor drugs. A signature comprising four genes associated with pyroptosis offers a novel approach to the prognosis and survival of patients with CM and will facilitate the development of individualized therapy.