PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

Abstract

Background Some studies have reported that the activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1, as a critical ribosome has been rarely reported in human tumors. Thus, the roles of PNO1 in HCC should be explored. Methods We collected 150 formalin-fixed and paraffin-embedded (FFPE) samples and 8 fresh samples to explore the expression and prognosis of PNO1 in HCC by immunohistochemistry, Western Blotting and RT-PCR. Public databases (TCGA and GEO) were used to verify the expression and prognosis. The functions of PNO1 in HCC was verified by in vitro and in vivo experiments. The underlying molecular mechanisms of PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results PNO1 expression was considerably higher in HCC tissues and the higher expression of PNO1 was associated with poor prognosis of HCC patients. In vitro experiments indicated that PNO1 overexpression promoted proliferation and depressed apoptosis of HCC cells. In addition, high expression of PNO1 increased autophagy of HCC cells. Consistent results were also observed in vivo experiments. The results of the RNA-seq analysis indicted that PNO1 as an oncogene promoted HCC progression through the MAPK signaling pathway. The results were also verified by in vivo experiments. Conclusions PNO1 was overexpressed in HCC, promoted autophagy and inhibited apoptosis of HCC cells via the MAPK signaling pathway.

PNO1 inhibits autophagy-mediated ferroptosis by GSH metabolic reprogramming in hepatocellular carcinoma

“…3E). Taken together, the results suggested that PNO1 promote autophagy in HCC, consistence with our previous study [15]. To determine whether PNO1-mediated autophagy is related to ferroptotic cell death in HCC cancer cells, we used rapamycin or CQ co-treated with erastin to verify cell viability and cell death through CCK8 (Fig.…”

“…Our previous study has shown that PNO1 is associated with the progression of various cancers, including HCC [15] and lung adenocarcinoma [16]. We further explored the molecular mechanism of PNO1 in regulating the malignant progression of HCC by performing differential protein enrichment analysis, which suggested that PNO1 was significantly associated with ferroptosis (Fig.…”

“…In addition, studies shown that the metabolism of glutamate is related to ferroptosis [24], and high level of intracellular glutamate could enhance system Xcactivity [25]. In our previous study, we investigated that PNO1 promote autophagy in HCC via the MAPK signaling pathway [15]. Mukhopadhyay et al found that autophagy inhibition diminished the activity of system Xcin PDAC [26].…”

Scoparone inhibits the growth of liver cancer cells by regulating MAPK signaling pathway

“…Several proteins and drugs affect the progression and metastasis of liver cancer via this pathway. For example, PNO1 mediated the autophagy and apoptosis of liver cancer via this pathway [20]. EB2 also promoted liver cancer proliferation and metastasis via MAPK pathway by regulating microtubule dynamics [21].…”

RNA m6A methyltransferase METTL14 promotes the procession of non‐small cell lung cancer by targeted CSF1R

“…Equal amounts of protein were loaded on gels and separated by SDS‐PAGE. Then, proteins were transferred to PVDF membranes (Immobilon‐P; Millipore) and blocked with 5% milk or bovine serum albumin, followed by incubation with primary and secondary antibodies 23 . Primary antibodies were METTLE14 (1:2000, CST, 51104), CSF1R (1:1000, abcam, ab229188), and GAPDH (1:10000, abcam, ab181602) antibodies.…”