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RNA modification plays important roles in various physiological and pathological process. LAGE3 is a component of EKC/KEOPS complex, which is probably involved in the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs, but its exact role in HCC is less studied. Our study reveals that LAGE3 exhibits upregulated expression in HCC compared with normal hepatocellular tissue. High expression of LAGE3 promotes hepatocellular cell proliferation and migration. Further investigations suggest that the increased expression of LAGE3 cloud lead to upregulated VEGFA secretion and angiogenesis in HCC. The mechanistic study reveals LAGE3 is required for the VEGFA mRNA stability. This research may open new avenues for diagnosis and targeted therapy in HCC., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

STK19 was originally identified as a manganese-dependent serine/threonine-specific protein kinase, but its function has been highly debated. Here, the crystal structure of STK19 revealed that it does not contain a kinase domain, but three intimately packed winged helix (WH) domains. The third WH domain mediated homodimerization and double-stranded DNA binding, both being important for its nuclear localization. STK19 participated in the nucleotide excision repair (NER) and mismatch repair (MMR) pathways by recruiting damage repair factors such as RPA2 and PCNA. STK19 also bound double-stranded RNA through the DNA-binding interface and regulated the expression levels of many mRNAs. Furthermore, STK19 knockdown cells exhibited very slow cell proliferation, which cannot be rescued by dimerization or DNA-binding mutants. Therefore, this work concludes that STK19 is highly unlikely to be a kinase but a DNA/RNA-binding protein critical for DNA damage repair (DDR) and cell proliferation. To prevent further confusions, we renamed this protein as TWH19 (Tandem Winged Helix protein formerly known as STK19)., (© 2024 Li et al.)

Stem cells have the ability of self-replication and multidirectional differentiation, but the mechanism of how stem cells "maintain" this ability and how to "decide" to give up this state and differentiate into cells with specific functions is still unknown. The Nobel Prize in physiology and medicine in 2021 was awarded to "temperature and tactile receptor," which made the pain receptor TRPV1-calcitonin gene-related peptide (CGRP) pathway active again. The activation and blocking technology of CGRP has been applied to many clinical diseases. CGRP gene has complex structure and transcription process, with multiple methylation and other modification sites. It has been considered as a research hotspot and difficulty since its discovery. Drug manipulation of TRPV1 and inhibition of CGRP might improve metabolism and prolong longevity. However, whether the TRPV1-neuropeptide-CGRP pathway is directly or indirectly involved in stem cell self-replication and multidirectional differentiation is unclear. Recent studies have found that CGRP is closely related to the migration and differentiation of tumor stem cells, which may be realized by turning off or turning on the CGRP gene expression in stem cells and activating a variety of ways to regulate stem cell niches. In this study, we reviewed the advances in researches concentrated on the biological effects of CGRP as a new endogenous switching of cell stemness., Competing Interests: The authors have no competing interests to declare., (Copyright © 2022 Xiaoting Lv et al.)

Esophageal squamous cell carcinoma (ESCC) has one of the highest mortality rates worldwide. AU-rich element RNA-binding factor 1 (AUF1) is an established RNA-binding protein. AUF1 influences the process of development, apoptosis and tumorigenesis via interacting with adenylate-uridylate rich elements (AREs) bearing mRNAs. However, the clinical relevance of AUF1 and its biological function in ESCC progression have not been reported. In the present study, we first investigated the expression of AUF1 in the ESCC tissue samles and normal samples. We found a significantly higher expression of AUF1 in ESCC tissues than that in normal tissues and tumor adjacent tissues. The expression of AUF1 correlated with ESCC stage (P=0.011) and marginally correlated with lymph node metastasis (P=0.055) of ESCC patients. Silencing of AUF1 by an siRNA inhibited the proliferation and enhanced the apoptosis of ESCC cells. mRNA profiling by microarray analysis revealed that AUF1 knockdown affected 285 genes (fold change ≥2) that function in multiple pathways. GTP cyclohydrolase I (GCH1), the rate limiting enzyme for BH4 synthesis, was found to be downregulated. One of the AU-rich elements in the 3'UTR of GCH1 was found to be responsive to AUF1 expression by luciferase assay. Knockdown of GCH1 suppressed cell proliferation and colony formation of ESCC cells. The expression of AUF1 significantly correlated with that of GCH1 in ESCC tissues. Taken together, we demonstrated the overexpression of AUF1 in esophageal carcinoma and identified GCH1 as AUF1's effector for the proliferation of ESCC cells.

Radioresistance has been an important factor in restricting efficacy of radiotherapy for non-small cell lung cancer (NSCLC) patients and new approaches to inhibit cancer growth and sensitize irradiation were warranted. Despite the important role of ubiquitin/proteasome system (UPS) during cancer progression and treatment, the expression and biological role of ubiquitin (Ub) in human NSCLC has not been characterized. In this study, we found that ubiquitin was significantly overexpressed in 75 NSCLC tissues, compared to their respective benign tissues by immunohistochemistry (P < 0.0001). Knock-down of ubiquitin by mixed shRNAs targeting its coding genes ubiquitin B (UBB) and ubiquitin C (UBC) suppressed the growth and increased the radiosensitivity in NSCLC H1299 cells. Apoptosis and γ H2AX foci induced by X-ray irradiation were enhanced by knock-down of ubiquitin. Western blot and immunostaining showed that knock-down of ubiquitin decreased the expression and translocation of NF-κB to the nucleus by reduced phospho-IκBα after irradiation. Suppression of ubiquitin decreased the proliferation and radioresistance of H1299 transplanted xenografts in nude mice by promoting apoptosis. Taken together, our results demonstrate the critical role of ubiquitin in NSCLC proliferation and radiosensitivity. Targeting ubiquitin may serve as a potentially important and novel approach for NSCLC prevention and therapy.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to have antitumor effects. In some tumor models, the combination of celecoxib with chemotherapy agents has shown synergistic antitumor effect; however, the effect of celecoxib combination with tegafur/gimeracil/oteracil potassium on the malignant biological behaviors of gastric cancer in nude mice is unclear. In this study, female nude mice were subcutaneously transplanted with SGC-7901 gastric cancer cells. When the tumor model formed, the mice were divided into control group, celecoxib group, tegafur/gimeracil/oteracil potassium group, and the combination of both drug regimens group. Mice were treated for 3 weeks. Following treatment, the proliferating index was calculated, apoptosis related proteins, COX-2, vascular endothelial growth factor-C (VEGF-C) and lymphatic vessel density were quantified in tumor tissues by immunohistochemistry. Apoptosis was evaluated by TUNEL staining. The results revealed that celecoxib and tegafur/gimeracil/oteracil potassium alone significantly inhibited tumor growth. The combination of these two drugs showed a synergistic antitumor effect. Both celecoxib and tegafur/gimeracil/oteracil potassium alone inhibited proliferation and promoted apoptosis. The combination of these two drugs further enhanced this anticancer effect. Both celecoxib and the combination treatment inhibited lymphangiogenesis and the expression of COX-2 and VEGF-C. However, tegafur/gimeracil/oteracil potassium treatment had no obvious effect on lymphangiogenesis. These results suggested that the combination of celecoxib and tegafur/gimeracil/oteracil potassium produced a synergistic antitumor effect, possibly by inhibiting the proliferation of tumor cells and promoting apoptosis. Celecoxib and celecoxib in combination with tegafur/gimeracil/oteracil potassium possibly by reducing the expression of COX-2, in turn down-regulating the expression of VEGF-C, resulted in the inhibition of lymphangiogenesis.

To discuss the influence on proliferation and apoptosis of human intestinal epithelial cells by Helicobacter pylori (Hp). CCK-8 method and flow cytometry to test the influence on proliferation and apoptosis of intestinal epithelial cells by Hp and cell cycle distribution. Immunocytochemistry, qRT-PCR, and WB to analyze the expression and activation of ACVR1. Functional studies of TNBS-induced IBD on mice and DSS-induced IBD on C57BL/6J mice with HP used for intervention were also performed. Hp facilitated the proliferation of intestinal epithelial cells with the breeding ratios on the first and third day are 5.24% ± 3.26% and 34.18% ± 6.68% respectively. ACVR1 is activated and the expression of anti-apoptosis protein Bcl-2 and Bcl-XL is up-regulated. In vivo, TNBS-induced and Hp-induced exhibited inflammatory lesions of intestine, ACVR1 and Bcl-2 higher expressions as compared to wild-type mice. Hp is likely to play a very important role in the proliferation, apoptosis, and malignant transformation of intestinal epithelial cells through ACVR1 pathway. [ABSTRACT FROM AUTHOR]

Abstract: Both deregulation of tumor-suppressor genes and misexpression of microRNAs (miRNAs) have been implicated in the development of pancreatic cancer, but their relationship during this process remains less clear. Here, we report that the expression of miR-483-3p is strongly enhanced in pancreatic cancer tissues compared to side normal tissues using a miRNA-array differential analysis. Furthermore, DPC4/Smad4 is identified as a target of miR-483-3p and their expression levels are inversely correlated in human clinical specimens. Ectopic expression of miR-483-3p significantly represses DPC4/Smad4 protein levels in pancreatic cancer cell lines, and simultaneously promotes cell proliferation and colony formation in vitro. Our findings identify miR-483-3p as a potent regulator of DPC4/Smad4, which may provide a novel therapeutic strategy for the treatment of DPC4/Smad4-driven pancreatic cancer. [ABSTRACT FROM AUTHOR]

Natural medicine can be used to develop wound healing agents due to its excellent characteristics of promoting rapid wound healing. Pine pollen polysaccharides (PPPS), a water-soluble polysaccharide with hydrophilicity and viscosity, which is suitable for the development of wound dressing. The purpose of this study is to explore the role and mechanism of PPPS in the process of wound healing. The results showed that PPPS could accelerate the wound healing, promote cell proliferation, transform the cell cycle from G1 phase to S and G2 phase, and increase the expression of Cyclin B1 in vitro. These effects of PPPS were achieved by activating JAK2-STAT3 signaling pathway. Similarly, PPPS could accelerate the healing of mouse cutaneous wounds, and could promote the growth of chicken embryo chorioallantoic vessels. In conclusion, this study indicates that PPPS is a new promising natural agent for promoting wound healing. Diagram of the mechanism of PPPS promoting wound healing. [Display omitted] • Pine pollen polysaccharides accelerate wound healing by promoting cell proliferation. • Pine pollen polysaccharides activate JAK2-STAT3 signaling pathway to promote cell proliferation. • Pine pollen polysaccharides can promote the growth of blood vessels. [ABSTRACT FROM AUTHOR]