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Thyroid cancer (TC) has increased globally, with a prominent increase in small, papillary thyroid cancers. PEST-containing nuclear protein (PCNP), a nuclear protein, has been found to be associated with human cancers in recent years. However, the role and molecular mechanism of PCNP in thyroid cancer remain underexplored. In the present study, the results showed that the expression levels of PCNP in human thyroid tissues were higher than those in adjacent non-tumor tissues. Overexpression of PCNP reduced the proliferation, migration, and invasion of human thyroid cancer cells and down-regulation of PCNP showed reverse effects. In addition, PCNP regulated cell cycle arrest through modifications in the expression of cell cycle regulating genes and PCNP affected apoptosis via activation of ERK/JNK/p38 pathway in thyroid cancer cells. Moreover, PCNP overexpression promoted autophagy by reducing the expression levels of Wnt/β-catenin pathway in TC cells, however, PCNP knockdown had opposite effects. Furthermore, PCNP overexpression reduced the growth of xenografted human thyroid cancer, whereas PCNP knockdown showed opposite trends. In conclusion

Among urological tumors, renal cell carcinoma (RCC) is the third-highest mortality rate tumor, and 20%–30% of RCC patients present with metastases at the time of diagnosis. While the treatment of RCC has been improved over the last few years, its mortality stays high. Y-box binding protein 1 (YBX1) is a well-known oncoprotein that has tumor-promoting functions. YBX1 is widely considered to be an attractive therapeutic target in cancer. To develop novel therapeutics to target YBX1, it is of great importance to understand how YBX1 is finely regulated in cancer. Our previous studies showed that YBX1 in RCC cells significantly promoted cell adhesion, migration, and invasion. However, the role of YBX1 in RCC cells apoptosis has not been reported. In this study, we investigated the effect of YBX1 on cell apoptosis and elucidated the mechanisms involved. Results showed that YBX1 regulated RCC cells apoptosis and reactive oxygen species (ROS) generation via Kindlin-2. These findings indicated that YBX1 inhibited RCC cells apoptosis and may serve as a candidate RCC prognostic marker and a potential therapeutic target. Abbreviations: RCC: Renal cell carcinoma; YBX1: Y-box binding protein 1; ROS: Reactive oxygen species; ccRCC: Clear cell renal cell carcinoma; mccRCC: Metastatic clear cell renal cell carcinoma; G3BP1: Ras-GTPase activating protein SH3 domain-binding proteins 1; SPP1: Secreted phosphoprotein 1; NF-κB: Nuclear factor kappa beta; ECM: Extracellular matrix; EMT: Epithelial-mesenchymal transition; PYCR1: Pyrroline-5-carboxylate reductase 1; MEM: Eagle’s Minimum Essential Medium; DMEM: Dulbecco’s modified Eagle medium; FBS: Fetal bovine serum; PCR: Polymerase chain reaction; shRNA: Short hairpin RNA; siRNA: Small interfering RNA; BSA: Bovine serum albumin; DCFH-DA: 2,7-Dichlorodihydrofluorescein diacetate; FITC: Fluorescein isothiocyanate; PI: Propidium iodide

Methamphetamine (METH) abuse can result in severe neurotoxicity, for which the mechanism is not yet clear. In the present study, we investigated the role of noncoding RNAs in METH-induced dopaminergic neurotoxicity, and analyzed the underlying mechanism using bioinformatic methods. We confirmed by flow cytometry that miR-129-1-3p is involved in promoting dopaminergic apoptosis under METH treatment and its role could be inhibited by a high concentration of circ_0015891. Also, we combined transcriptomic data with bioinformatics to explore the downstream mechanism of miR-129-1-3p regulation of METH-induced apoptosis, highlighted the potentially pivotal figure of response to nutrition. Further bioinformatic analysis of circ_0015891 was conducted as well and showed that circ_0015891 was the sponge of various microRNAs that effect apoptosis by different mechanisms. Collectively, we found a novel circ_0015891/miR-129-1-3p axis that may be a promising therapeutic target for METH-induced dopaminergic neurotoxicity.

Bufonis (VB), an animal drug called Chansu in China, is the product of the secretion of Bufo gargarizans Cantor or B. melanostictus Schneider. As a traditional Chinese medicine (TCM) for a long time, it has been widely used in the treatment of heart failure, ulcer, pain, and various cancers. Cinobufaginn (CNB), the cardiotonic steroid or bufalene lactone extracted from VB, has the effects of detoxification, detumescence, and analgesia.The present study aimed to define the effects of CNB on non-small-cell lung cancer (NSCLC) and identify the potential molecular mechanisms.A549 cells were treated with cinobufagin and cell viability, apoptosis, migration, and invasion were then evaluated using Cell Counting Kit-8 (CCK8) assays, flow cytometry, and Transwell assays, respectively. Moreover, the levels of proliferating cell nuclear antigen (PCNA), cytokeratin8 (CK8), poly ADP-ribose polymerase (PARP), Caspase3, Caspase8, B-cell lymphoma/lewkmia-2(Bcl-2), Bcl2-Associated X(Bax), forkhead box O1 (FOXO1), and euchromatic histone-lysine N-methyltransferase2 (G9a, EHMT2) in A549 cells were evaluated using qRT-PCR and/or Western blot analysis (WB), Co-IP, immunofluorescence, and immunohistochemistry. An in vivo imaging system, TUNEL, Immunofluorescence, and immunohistochemistry were also used to detect proliferating cell nuclear antigen(PCNA), Ki67, E-Cadherin(E-Cad), FOXO1, and G9a in mouse xenograft model experiments.CNB suppressed cell proliferation, migration, and invasion but promoted apoptosis in A549 cells in a dose- and time-dependent manner, while cinobufagin had no cytotoxic effect on BEAS-2B cells. In vivo, cinobufagin inhibited the proliferation, migration, and invasion of A549 cells and promoted their apoptosis. The occurrence of the above phenomena was accompanied by an increase in FOXO1 expression and a decrease in G9a expression. In A549 cells, CNB did not reverse the changes in the proliferation, migration, invasion, and apoptosis of A549 cells after FOXO1 was successfully silenced.Our study provides the first evidence that cinobufagin suppresses the malignant biological behaviours of NSCLC cells in vivo and in vitro and suggests that mechanistically, this effect may be achieved by inhibiting the expression of the histone methyltransferase G9a and activating the tumour suppressor gene FOXO1. Taken together, our findings provide important insights into the molecular mechanism underlying cinobufagin's anticancer activity, and suggest that cinobufagin could be a candidate for targeted cancer therapy.