Suppression of Ribose-5-Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer

Abstract

Ribose-5-phosphate isomerase A (RPIA) regulates tumorigenesis in liver and colorectal cancer. However, the role of RPIA in lung cancer remains obscure. Here we report that the suppression of RPIA diminishes cellular proliferation and activates autophagy, apoptosis, and cellular senescence in lung cancer cells. First, we detected that RPIA protein was increased in the human lung cancer versus adjust normal tissue via tissue array. Next, the knockdown of RPIA in lung cancer cells displayed autophagic vacuoles, enhanced acridine orange staining, GFP-LC3 punctae, accumulated autophagosomes, and showed elevated levels of LC3-II and reduced levels of p62, together suggesting that the suppression of RPIA stimulates autophagy in lung cancer cells. In addition, decreased RPIA expression induced apoptosis by increasing levels of Bax, cleaved PARP and caspase-3 and apoptotic cells. Moreover, RPIA knockdown triggered cellular senescence and increased p53 and p21 levels in lung cancer cells. Importantly, RPIA knockdown elevated reactive oxygen species (ROS) levels. Treatment of ROS scavenger N-acetyl-L-cysteine (NAC) reverts the activation of autophagy, apoptosis and cellular senescence by RPIA knockdown in lung cancer cells. In conclusion, RPIA knockdown induces ROS levels to activate autophagy, apoptosis, and cellular senescence in lung cancer cells. Our study sheds new light on RPIA suppression in lung cancer therapy.

Thermal impacts on transcriptome of Pectoralis major muscle collected from commercial broilers, Thai native chickens and its crossbreeds

“…Increased CBS and GSTA4 abundance in the stressed BR might imply an autocorrective function of CBS to oxidative condition through glutathione system [ 17 ]. As for RPIA, the enzyme catalyzes the process of histidine biosynthesis and formation of nucleotides or glycolytic intermediates depending on body condition [ 18 ]. The crucial role of RPIA in mediating ROS level, apoptosis and autophagy was addressed in lung cancer cells [ 18 ].…”

“…As for RPIA, the enzyme catalyzes the process of histidine biosynthesis and formation of nucleotides or glycolytic intermediates depending on body condition [ 18 ]. The crucial role of RPIA in mediating ROS level, apoptosis and autophagy was addressed in lung cancer cells [ 18 ]. Furthermore, differential expression of gene encoding glutamine-fructose-6-phosphate aminotransferase (isomerizing) 2 isoform X2 ( GFPT2 , log 2 FC = −1.1) suggested the altered hexosamine pathways in the thermal-stressed BR.…”

Single‐cell RNA sequencing reveals blastomere heterogeneity of 2‐cell embryos in pigs

“…PRPF40A (Pre-mRNA processing factor 40 homologue A) is a pre-mRNA splicing protein, which has been reported as a cancer marker (Huo et al, 2019). RPIA (ribose-5-phosphate isomerase A) regulates autophagy, apoptosis and cell cycle to mediate tumorigenesis (Nieh et al, 2022).…”

“…PRPF40A (Pre‐mRNA processing factor 40 homologue A) is a pre‐mRNA splicing protein, which has been reported as a cancer marker (Huo et al, 2019). RPIA (ribose‐5‐phosphate isomerase A) regulates autophagy, apoptosis and cell cycle to mediate tumorigenesis (Nieh et al, 2022). Further biological prediction of functional elements identified different numbers of PASs or CPEs in varied 3′UTRs of HSDL2, SGTA, FAM204A, PSPH, PRPF40A and RPIA.…”

Characterizing the ovarian response to xenobiotic and environmentally induced metabolic challenges

“…Reduced abundance of ribose-5-phosphate isomerase A (RPIA), a key regulator of the pentose phosphate pathway was observed. Little information is found in the literature of possible roles of RPIA in the ovary, however, suppression of RPIA by knockdown in lung and endothelial cancer cells is demonstrated to inhibit cell growth by mediating mitochondria apoptosis and autophagy (Szwarc et al, 2018;Nieh et al, 2022), reducing glycolytic capacity and oxidative phosphorylation. Thus, activation of RPIA by ZEN in TN gilts suggest that ZEN may drive glycolysis, with HS reducing the metabolic rate of glycolysis and possibly inducing cell death.…”