BackgroundPEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated.MethodsShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo.ResultsPCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis.ConclusionsPCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

Diaphragm dysfunction is an important clinical problem worldwide. Hydrogen sulfide (H2S) is involved in many physiological and pathological processes in mammals. However, the effect and mechanism of H2S in diaphragm dysfunction have not been fully elucidated. In this study, we detected that the level of H2S was decreased in lipopolysaccharide- (LPS-) treated L6 cells. Treatment with H2S increased the proliferation and viability of LPS-treated L6 cells. We found that H2S decreased reactive oxygen species- (ROS-) induced apoptosis through the mitogen-activated protein kinase (MAPK) signaling pathway in LPS-treated L6 cells. Administration of H2S alleviated LPS-induced inflammation by mediating the toll-like receptor-4 (TLR-4)/nuclear factor-kappa B (NF-κB) signaling pathway in L6 cells. Furthermore, H2S improved diaphragmatic function and structure through the reduction of inflammation and apoptosis in the diaphragm of septic rats. In conclusion, these findings indicate that H2S ameliorates LPS-induced diaphragm dysfunction in rats by reducing apoptosis and inflammation through ROS/MAPK and TLR4/NF-κB signaling pathways. Novel slow-releasing H2S donors can be designed and applied for the treatment of diaphragm dysfunction.

Lung cancer is the leading cause of cancer-related mortality worldwide. PEST-containing nuclear protein (PCNP) has been found in the nucleus of cancer cells. Whether PCNP plays a role in the growth of lung adenocarcinoma is still unknown. In the present study, the results indicated that the level of PCNP in lung adenocarcinoma tissue was significantly higher than that in corresponding adjacent non-tumor tissue. Over-expression of PCNP promoted the proliferation, migration, and invasion of lung adenocarcinoma cells, while down-regulation of PCNP exhibited opposite effects. PCNP over-expression decreased apoptosis through up-regulating the expression levels of phospho (p)-signal transducers and activators of transcription (STAT) 3 and p-STAT5 in lung adenocarcinoma cells, whereas PCNP knockdown showed opposite trends. PCNP overexpression enhanced autophagy by increasing the expression levels of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) in lung adenocarcinoma cells, however an opposite trend was observed in the sh-PCNP group. In addition, overexpression of PCNP showed the tumor-promoting effect on xenografted lung adenocarcinoma, while PCNP knockdown reduced the growth of lung adenocarcinoma via regulating angiogenesis. Our study elucidates that PCNP can regulate the procession of human lung adenocarcinoma cells via STAT3/5 and PI3K/Akt/mTOR signaling pathways. PCNP may be considered as a promising biomarker for the diagnosis and prognosis in patients with lung adenocarcinoma. Furthermore, PCNP can be a novel therapeutic target and potent PCNP inhibitors can be designed and developed in the treatment of lung adenocarcinoma.

Tumour necrosis factor‐α‐induced protein 8‐like 2 (TIPE2) is a tumour suppressor in many types of cancer. However, the mechanism of action of TIPE2 on the growth of rectal adenocarcinoma is unknown. Our results showed that the expression levels of TIPE2 in human rectal adenocarcinoma tissues were higher than those in adjacent non‐tumour tissues. Overexpression of TIPE2 reduced the proliferation, migration, and invasion of human rectal adenocarcinoma cells and down‐regulation of TIPE2 showed reverse effects. TIPE2 overexpression increased apoptosis through down‐regulating the expression levels of Wnt3a, phospho (p)‐β‐Catenin, and p‐glycogen synthase kinase‐3β in rectal adenocarcinoma cells, however, TIPE2 knockdown exhibited reverse trends. TIPE2 overexpression decreased autophagy by reducing the expression levels of p‐Smad2, p‐Smad3, and transforming growth factor‐beta (TGF‐β) in rectal adenocarcinoma cells, however, TIPE2 knockdown showed opposite effects. Furthermore, TIPE2 overexpression reduced the growth of xenografted human rectal adenocarcinoma, whereas TIPE2 knockdown promoted the growth of rectal adenocarcinoma tumours by modulating angiogenesis. In conclusion, TIPE2 could regulate the proliferation, migration, and invasion of human rectal adenocarcinoma cells through Wnt/β‐Catenin and TGF‐β/Smad2/3 signalling pathways. TIPE2 is a potential therapeutic target for the treatment of rectal adenocarcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. Peptide V3 has shown anti-angiogenic and anti-tumor effects on S180 and H22 xenografts in nude mice. However, the detailed mechanism of action of peptide V3 has not yet been fully elucidated. In the present study, the effects of peptide V3 on the growth of human HCC cells were examined both in vitro and in vivo . Our results showed that peptide V3 inhibited the proliferation, viability, migration, and invasion of human HCC cells. However, no obvious effect was observed in HL-7702 cells. Peptide V3 increased the apoptosis and decreased the protein levels of H-RAS, phospho (p)-RAF, p-MEK, and p-extracellular signal-regulated protein kinase (ERK) in human HCC cells. Peptide V3 suppressed the growth of human HCC xenografts by down-regulating angiogenesis and up-regulating apoptosis. In conclusion, peptide V3 could inhibit the growth of human HCC by inhibiting the Ras/Raf/MEK/ERK signaling pathway. Novel peptides and modification strategies could be designed and applied for the treatment of different types of cancer.