The p53‐inducible long noncoding RNA TRINGS protects cancer cells from necrosis under glucose starvation

Abstract

The tumor suppressor p53 is activated in response to cellular stress to prevent malignant transformation. However, several recent studies have shown that p53 can play protective roles in tumor cell survival under adversity. Whether p53-regulated long noncoding RNAs are involved in this process remains to be fully understood. Here, we show that under glucose starvation condition, p53 directly upregulates a novel lncRNA named TRINGS (Tp53-regulated inhibitor of necrosis under glucose starvation) in human tumor cells. TRINGS binds to STRAP and inhibits STRAP-GSK3b-NF-jB necrotic signaling to protect tumor cells from cell death. Interestingly, TRINGS appears to respond to glucose starvation specifically, as it is not activated by serum, serine, or glutamine deprivation. Collectively, our findings reveal that p53-induced lncRNA TRINGS controls the necrotic pathway and contributes to the survival of cancer cells harboring wild-type p53 under glucose stress.

LncRNA TP73-AS1 Promotes Cell Proliferation and Inhibits Cell Apoptosis in Clear Cell Renal Cell Carcinoma Through Repressing KISS1 Expression and Inactivation of PI3K/Akt/mTOR Signaling Pathway

“…In addition, we unexpectedly found that the cell necrosis was at some extent increased when overexpression of TP73-AS1 while knockdown of it lead to the opposite result (data not shown). Although the role of other lncRNAs on cell necrosis have been reported [29], whether TP73-AS1 could mTOR expression, while overexpression of KISS1 partly reversed these trends. (F) CCK8 assay showed that TP73-AS1 knockdown induced inhibition of cell proliferation was alleviated by treatment with PI3K inhibitor (LY294002) or mTOR inhibitor (CCI-779) [30,31].…”

ELK1‐activated GPC3‐AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells

“…Increasing studies focus on the function and underlying mechanism of long non‐coding RNA (lncRNA) in human tumors . As a member of non‐coding RNA (ncRNA) family, lncRNA is defined as the RNA transcripts with a length > 200 nucleotides, which is differentiated from other ncRNAs, such as microRNA and transfer RNA .…”

“…6 Increasing studies focus on the function and underlying mechanism of long non-coding RNA (lncRNA) in human tumors. [7][8][9] As a member of non-coding RNA (ncRNA) family, lncRNA is defined as the RNA transcripts with a length > 200 nucleotides, which is differentiated from other ncRNAs, such as microRNA and transfer RNA. [10][11][12][13][14] In general, lncRNA is classified into five groups based on the different gene locations, including antisense lncRNA, intronic transcript, large intergenic noncoding RNA, promoter-associated lncRNA and UTR associated lncRNA.…”

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

“…Long non‐coding RNAs, a subset of non‐coding transcripts with more than 200 nucleotides in length, have been shown to play important roles in numerous biological processes, for example inflammation, immunity and various cancers . With the development of high throughput RNA sequencing approach, a variety of novel lncRNAs were identified.…”

“…Long non-coding RNAs, a subset of non-coding transcripts with more than 200 nucleotides in length, have been shown to play important roles in numerous biological processes, for example inflammation, immunity and various cancers. [22][23][24][25] With the development of high throughput RNA sequencing approach, a variety of novel lncRNAs were identified. However, due to the tissue specific and low expression properties, functional involvement of a majority of lncRNAs remains unclear, up to date.…”