P21 is a protein secreted by all forms of Trypanosoma cruzi (T. cruzi) with recognized biological activities determined in studies using the recombinant form of the protein. In our recent study, we found that the ablation of P21 gene decreased Y strain axenic epimastigotes multiplication and increased intracellular replication of amastigotes in HeLa cells infected with metacyclic trypomastigotes. In the present study, we investigated the effect of P21 in vitro using C2C12 cell lines infected with tissue culture-derived trypomastigotes (TCT) of wild-type and P21 knockout (TcP21-/-) Y strain, and in vivo using an experimental model of T. cruzi infection in BALB/c mice. Our in-vitro results showed a significant decrease in the host cell invasion rate by TcP21-/- parasites as measured by Giemsa staining and cell count in bright light microscope. Quantitative polymerase chain reaction (qPCR) analysis showed that TcP21-/- parasites multiplied intracellularly to a higher extent than the scrambled parasites at 72h post-infection. In addition, we observed a higher egress of TcP21-/- trypomastigotes from C2C12 cells at 144h and 168h post-infection. Mice infected with Y strain TcP21-/- trypomastigotes displayed higher systemic parasitemia, heart tissue parasite burden, and several histopathological alterations in heart tissues compared to control animals infected with scrambled parasites. Therewith, we propose that P21 is important in the host-pathogen interaction during invasion, cell multiplication, and egress, and may be part of the mechanism that controls parasitism and promotes chronic infection without patent systemic parasitemia.

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

Filopodia, widely distributed on cell surfaces, are distinguished by their dynamic extensions, playing pivotal roles in a myriad of biological processes. Their functions span from mechanosensing and guidance to cell-cell communication during cellular organization in the early embryo. Filopodia have significant roles in pathogenic processes, such as cancer invasion and viral dissemination. Molecular mapping of the filopodome has revealed generic components essential for filopodia functions. In parallel, recent insights into biophysical mechanisms governing filopodia dynamics have provided the foundation for broader investigations of filopodia\'s biological functions. We highlight recent discoveries of engagement of filopodia in various stages of development and pathogenesis and present an overview of intricate molecular and physical features of these cellular structures across a spectrum of cellular activities.

Increasing evidence suggests a significant association between periodontal disease and the occurrence of various cancers. The carcinogenic potential of several periodontal pathogens has been substantiated in vitro and in vivo. This review provides a comprehensive overview of the diverse mechanisms employed by different periodontal pathogens in the development of cancer. These mechanisms induce chronic inflammation, inhibit the host\'s immune system, activate cell invasion and proliferation, possess anti-apoptotic activity, and produce carcinogenic substances. Elucidating these mechanisms might provide new insights for developing novel approaches for tumor prevention, therapeutic purposes, and survival improvement.

Glioma, a formidable form of brain cancer, poses significant challenges in terms of treatment and prognosis. Circular RNA nucleoporin 98 (circNUP98) has emerged as a potential regulator in various cancers, yet its role in glioma remains unclear. Here, we elucidate the functional role of circNUP98 in glioma cell proliferation, invasion, and migration, shedding light on its therapeutic implications. Glioma cells were subjected to si-NUP98 transfection, followed by assessments of cell viability, proliferation, invasion, and migration. Subcellular localization of circNUP98 was determined, and its downstream targets were identified. We delineated the binding relationships between circNUP98 and microRNA (miR)-520f-3p, as well as between miR-520f-3p and ETS transcription factor ELK4 (ELK4). The expression levels of circNUP98/miR-520f-3p/ELK4 were quantified. Our findings demonstrated that circNUP98 was upregulated in glioma cells, and its inhibition significantly attenuated glioma cell proliferation, invasion, and migration. Mechanistically, circNUP98 functioned as a sponge for miR-520f-3p, thereby relieving the inhibitory effect of miR-520f-3p on ELK4. Moreover, inhibition of miR-520f-3p or overexpression of ELK4 partially rescued the suppressive effect of circNUP98 knockdown on glioma cell behaviors. In summary, our study unveils that circNUP98 promotes glioma cell progression via the miR-520f-3p/ELK4 axis, offering novel insights into the therapeutic targeting of circNUP98 in glioma treatment.

In eukaryotes, Hsp90B1 serves as a vital chaperonin, facilitating the accurate folding of proteins. Interestingly, Hsp90B1 exhibits contrasting roles in the development of various types of cancers, although the underlying reasons for this duality remain enigmatic. Through the utilization of the Drosophila model, this study unveils the functional significance of Gp93, the Drosophila ortholog of Hsp90B1, which hitherto had limited reported developmental functions. Employing the Drosophila cell invasion model, we elucidated the pivotal role of Gp93 in regulating cell invasion and modulating c-Jun N-terminal kinase (JNK) activation. Furthermore, our investigation highlights the involvement of the unfolded protein response-associated IRE1/XBP1 pathway in governing Gp93 depletion-induced, JNK-dependent cell invasion. Collectively, these findings not only uncover a novel molecular function of Gp93 in Drosophila, but also underscore a significant consideration pertaining to the testing of Hsp90B1 inhibitors in cancer therapy.

This research investigated the anticancer properties of punicalagin, a prominent bioactive polyphenol extracted from Punica granatum L, in human gastric cancer cell lines. Normal and gastric cancer cells were exposed to different doses of punicalagin for various durations. Punicalagin exhibited cytotoxic effects on gastric cancer cells in a dose- and time-dependent fashion, while sparing normal gastric epithelial cells. It is noteworthy that among the 3 gastric cancer cells, HGC-27 cells were more resistant to punicalagin than 23,132/87 and AGS cells. Furthermore, punicalagin triggered apoptosis in gastric cancer cells, evidenced by a rise in both early and late apoptotic cell percentages. Western blot analysis further revealed that punicalagin elevated the levels of activated caspase-3. Conversely, punicalagin curtailed cell invasion and reduced the expression of MMP-2, MMP-9, Snail, and Slug. From a mechanistic standpoint, Western blotting indicated that punicalagin might inhibit the Erk and NF-κB pathways, leading to apoptosis induction and the inhibition of cell invasion in gastric cancer cells. These results indicate that punicalagin promotes apoptosis and inhibits cell invasion in gastric cancer cells by activating caspase-3 and suppressing MMP-2, MMP-9, Snail, and Slug through the inhibition of the Erk and NF-κB pathways.

BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) is increasing, and more effective treatment protocols must rapidly be developed to prevent the death of patients and ensure favorable outcomes. CircRNAs are a unique class of noncoding ribonucleic acid (RNA) molecules unaffected by RNA exonucleases. CircRNAs have more stable expression than linear RNAs and are not readily degraded; therefore, they are the newest focus of RNA research. Here, we analyze the mechanism of hsa_circ_0004771 (circ_0004771) in OSCC to provide a clinical reference.
METHODS: Circ_0004771 expression was measured in peripheral blood, cancerous tissues and adjacent tissues of OSCC patients. Patients were followed up for 3 years. The diagnostic value of circ_0004771 for OSCC occurrence, prognosis, recurrence and survival was analyzed with receiver operating characteristic (ROC) curves. OSCC cells were lentivirally transduced with a circ_0004771-silencing or an empty vector to evaluate alterations in cell growth, invasion, and apoptosis. Apoptosis-related and epithelial-mesenchymal transition (EMT)-related protein expression was quantified. BALB/c nude mice were used for tumorigenesis experiments to evaluate tumor growth in vivo after silencing circ_0004771.
RESULTS: Circ_0004771 expression was higher in peripheral blood and cancerous tissue of OSCC patients than in control peripheral blood and paracancerous tissue, respectively, exhibiting excellent predictive value for OSCC occurrence, prognosis, recurrence and survival. Silencing circ_0004771 decreased the growth, invasiveness, and EMT capacity and increased the apoptosis of OCC cells. In mice implanted with OSCC cells transduced with the circ_0004771-silencing lentiviral vector, the tumor growth capacity was obviously decreased.
CONCLUSIONS: Silencing circ_0004771 inhibits the malignant growth of OSCC.

BACKGROUND: Cepharanthine, a bioactive constituent of Stephania japonica (Thunb.) Miers, is known for its potent anti-tumor properties. Nevertheless, the precise impact of this substance on bladder cancer remains poorly comprehended. The aim of this study was to demonstrate the effect and mechanism of cepharanthine on the metastasis of human bladder cancer cells.
METHODS: The application of network pharmacology was utilized to ascertain the possible targets and signaling pathways of cepharanthine in the treatment of bladder cancer. The antiproliferative effects of cepharanthine were evaluated using Cell Counting Kit-8 and colony formation assays. The migration and invasion capabilities were assessed using Transwell assays and wound healing experiments. Proteins related to the Rap1 signaling pathway, cellular migration, cellular invasion, and Epithelial-Mesenchymal Transition (EMT) were quantified by western blotting.
RESULTS: Through database screening, 313 cepharanthine-acting targets, 277 candidate disease targets in bladder cancer, 22 intersecting targets, and 12 core targets were confirmed. The involvement of the Rap1 signaling system was revealed by the Kyoto Encyclopedia of Genes and Genomes\' pathway enrichment study. Cepharanthine was shown to decrease bladder cancer cell proliferation, migration, and invasion in vitro. Cepharanthine activated the Rap1 signaling pathway by upregulating Epac1 and downregulating E-cadherin and C3G protein expression, leading to increased expression of Rap1 GTP protein and decreased expression of protein kinase D1 and integrin α5. Rap1 signalling pathway activation resulted in the downregulation of migration and invasion-related proteins, matrix metallopeptidase MMP2, MMP9, as well as EMT-related proteins, N-cadherin and Snail, without affecting vimentin expression.
CONCLUSIONS: Cepharanthine inhibits migration, invasion, and EMT of bladder cancer cells by activating the Rap1 signalling pathway. The results offer helpful insights regarding the possible therapeutic use of cepharanthine for treating bladder cancer.

Subsequently to the publication of the above paper, the authors drew to the attention of the Editorial Office that they made a couple of errors in terms of the data assembly in Figs. 2 and 4 in their paper; specifically, the Transwell assay data shown for the \'miR-320a+/FoxM1+\' panel in Fig. 5D on p. 1923 also appeared as the \'ACTN/NC\' data panel in Fig. 4E on the same page (Fig. 4E contained the erroneously duplicated panel). In addition, data featured in Fig. 2D of the above paper were strikingly similar to data that appeared in Fig. 6e of the following paper, published subsequently to this article, written by different authors (although a Dr Shiyue Zhao worked in the molecular biology laboratory of Harbin Medical University from 2017 to 2018, and the research collaboration was conducted with Dr Chenlong Li\'s research group): Li C, Zheng H, Hou W, Bao H, Xiong J, Che W, Gu Y, Sun H and Liang P: Long non-coding RNA linc00645 promotes. TGF-β-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 10: 17, 2019. Finally, after having conducted an independent investigation of the data in this paper, the Editorial Office noted that one of the Petri dish images in Fig. 2C was also strikingly similar to data that appeared in Fig. 2H of the abovementioned article in the journal Cell Death & Disease. After having considered the authors\' request for corrigendum, in view of the problems that were identified with the data, the Editor of Oncology Reports has decided that, owing to a lack of confidence in the presented data, the paper should instead be retracted from the journal. After having informed the authors of this decision, they accepted the decision to retract this paper. The Editor apologizes to the readership for any inconvenience caused.  [Oncology Reports 40: 1917‑1926, 2018; DOI: 10.3892/or.2018.6597].