LAMTOR5-AS1 regulates chemotherapy-induced oxidative stress by controlling the expression level and transcriptional activity of NRF2 in osteosarcoma cells

Abstract

Long-noncoding RNAs (lncRNAs) play roles in regulating cellular functions. High-throughput sequencing analysis identified a new lncRNA, termed LAMTOR5-AS1, the expression of which was much higher in the chemosensitive osteosarcoma (OS) cell line G-292 than in the chemoresistant cell line SJSA-1. Further investigations revealed that LAMTOR5-AS1 significantly inhibits the proliferation and multidrug resistance of OS cells. In vitro assays demonstrated that LAMTOR5-AS1 mediates the interaction between nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2) and kelch-like ECH-associated protein 1 (KEAP1), which regulate the oxidative stress. Further mechanistic studies revealed that LAMTOR5-AS1 inhibited the ubiquitination degradation pathway of NRF2, resulting in a higher level of NRF2 but a loss of NRF2 transcriptional activity. High level of NRF2 in return upregulated the downstream gene heme oxygenase 1 (HO-1). Moreover, NRF2 controls its own activity by promoting LAMTOR5-AS1 expression, whereas the feedback regulation is weakened in drug-resistant cells due to high antioxidant activity. Overall, we propose that LAMTOR5-AS1 globally regulates chemotherapy-induced cellular oxidative stress by controlling the expression and activity of NRF2.

ANXA10 is a prognostic biomarker and suppressor of hepatocellular carcinoma: a bioinformatics analysis and experimental validation

“…Functional experiments showed that overexpression of ENTPD3-AS1 inhibited cell proliferation in renal cancer cell lines 64 . Pu et al found that LAMTOR5-AS1 could markedly impair the proliferation of osteosarcoma cells 65 . Lin et al found that Linc01278 inhibited the cell proliferation of papillary thyroid cancer by impelling apoptosis and mitigated the effects of cancer cells migration and invasion by regulating the EMT process 66 .…”

The analysis of the pyroptosis-related genes and hub gene TP63 ceRNA axis in osteosarcoma

“…Moreover, we used the starBase v2.0 database to predict that LAMTOR5-AS1 regulates the expression of TP63 in OS through the ceRNA mechanism in combination with hsa-miR-23a-3p. Pu et al (42) demonstrated that LAMTOR5-AS1 reduces OS cell growth and multidrug resistance in a considerable way. In this study, LAMTOR5-AS1 knockdown decreased the expression of cleaved-Caspase-1, cleaved-Caspase-3, cleaved-Caspase-4, cleaved-Caspase-8, GSDME, and GSDMD-N in OS cells, which demonstrated that the type and expression trend of pyroptosis marker proteins regulated by LAMTOR5-AS1 was consistent with those regulated by TP63.…”

Molecular Mechanisms Related to Responses to Oxidative Stress and Antioxidative Therapies in COVID-19: A Systematic Review

“…Similarly, PRDX4, PRDX1, and MGST1 all have antioxidant capacities with their ROS scavenging abilities [ 159 , 160 , 161 ]. LAMTOR5 mediates the interaction between NRF2 and KEAP1, which regulates oxidative stress, as shown in osteosarcoma cells [ 162 ]. It has been reported that defects in the FTL cause an increase in iron levels and, thus, oxidative stress, contributing to neurodegeneration in mice.…”