Long Noncoding RNA p53‐Stabilizing and Activating RNA Promotes p53 Signaling by Inhibiting Heterogeneous Nuclear Ribonucleoprotein K deSUMOylation and Suppresses Hepatocellular Carcinoma

Abstract

To identify hepatocellular carcinoma (HCC)‐implicated long noncoding RNAs (lncRNAs), we performed an integrative omics analysis by integrating mRNA and lncRNA expression profiles in HCC tissues. We identified a collection of candidate HCC‐implicated lncRNAs. Among them, we demonstrated that an lncRNA, which is named as p53‐stabilizing and activating RNA (PSTAR), inhibits HCC cell proliferation and tumorigenicity through inducing p53‐mediated cell cycle arrest. We further revealed that PSTAR can bind to heterogeneous nuclear ribonucleoprotein K (hnRNP K) and enhance its SUMOylation and thereby strengthen the interaction between hnRNP K and p53, which ultimately leads to the accumulation and transactivation of p53. PSTAR is down‐regulated in HCC tissues, and the low PSTAR expression predicts poor prognosis in patients with HCC, especially those with wild‐type p53. Conclusion: This study sheds light on the tumor suppressor role of lncRNA PSTAR, a modulator of the p53 pathway, in HCC.

LINC00346 Acts as a Competing Endogenous RNA Regulating Development of Hepatocellular Carcinoma via Modulating CDK1/CCNB1 Axis

“…In exploring the specific molecular mechanism of CDK1/CCNB1 in regulating cancer, Zhang et al revealed that CCNB1 could affect the cell cycle and apoptosis of pancreatic cancer cells by regulating p53 signaling pathway (Zhang H. et al, 2018). Qin G et al reported that the p53 signaling pathway may be regulated by multiple genes to affect the development of liver cells (Qin et al, 2019). In addition, KEGG pathway enrichment analysis (Figure 1B) showed that multiple DEGs, including CDK1/CCNB1, were enriched in the p53 signaling pathway.…”

“…Danhier et al (2010) have reported that CDK1/CyclinB1 inhibitor JNJ-7706621 and aurora kinase combined with paclitaxel can effectively treat transplantable liver cancer and inhibit tumor growth. In addition, studies have shown that CDK1 and CCNB1 have inhibitory effects on p53 signaling pathway as regulatory factors in HCC (Qin et al, 2019). Cell cyclin B1 (CCNB1) is an important cell cycle protein whose abnormal expression plays an important role in regulating cell cycle (Jin et al, 1998).…”

The role of long noncoding RNAs in hepatocellular carcinoma

“…LncRNA PRAL facilitates the interaction of p53 with HSP90 thus preventing the binding of p53 with MDM2, leading to the stabilization of p53 and the suppression of HCC growth [73]. Similarly, lncRNA PSTAR physically binds to hnRNP K protein and enhances its SUMOylation, which facilitates the formation of the p53-hnRNP K protein complex, thereby competitively blocking MDM2-dependent p53 protein degradation and inhibiting HCC cell proliferation [111]. 3) LncRNAs HOTAIR is capable of serving as a scaffold to bind with PRC2 and E3 ligase Mex3b simultaneously, facilitating the degradation of PRC2 and promoting HBV-induced HCC progression [112].…”

The Interaction Between lncRNA SNHG6 and hnRNPA1 Contributes to the Growth of Colorectal Cancer by Enhancing Aerobic Glycolysis Through the Regulation of Alternative Splicing of PKM

“…From the enrichment results of the ChIRP-MS analysis and the SNHG6-related genes identified above, we speculated that SNHG6 may be involved in the metabolic process of CRC by interacting with hnRNP proteins. It was reported that lncRNAs can interact with hnRNP proteins and induce hnRNP to splice and process mRNA in CRC, prostate cancer, and hepatocellular carcinoma (20,45,46). Therefore, we wanted to identify the molecule that was involved with SNHG6 and hnRNP protein complexes in CRC metabolism.…”