Background WD repeat and SOCS box containing protein 1 (WSB1) promotes tumor progression and metastasis; however, its role in the response to hyperthermia combined with chemoradiotherapy in cervical cancer remains unclear. Therefore, this study investigated the involvement of WSB1 and the c-Myc/Wnt/β-catenin axis in the antitumor effects of this combined treatment.Methods WSB1 expression was examined in multiple cervical cancer cell lines, and its functional roles were evaluated using the cell counting kit-8, colony formation, wound healing, Transwell migration/invasion, and apoptosis assays. The c-Myc-mediated transcriptional regulation of WSB1 was analyzed using chromatin immunoprecipitation and dual-luciferase reporter assays. Wnt/β-catenin signaling activity and DNA damage were assessed via western blotting and immunofluorescence. Antitumor efficacy was further evaluated in a cervical cancer xenograft model treated with hyperthermia, chemoradiotherapy, or both.Results WSB1 was highly expressed in both HeLa and SiHa cells and promoted proliferation, migration, and invasion, while inhibiting apoptosis. c-Myc directly transcriptionally activated WSB1, and WSB1 was required for c-Myc-driven activation of Wnt/β-catenin signaling, thereby forming a positive feedback loop. Combined hyperthermia and chemoradiotherapy markedly suppressed malignant phenotypes in vitro and tumor growth in vivo, increased DNA damage, and downregulated c-Myc, WSB1, and Wnt/β-catenin pathway components, with minimal systemic toxicity.Conclusions WSB1 acts as an oncogenic driver in cervical cancer by sustaining c-Myc/Wnt/β-catenin signaling across different histological subtypes. Axis disruption via combined hyperthermia and chemoradiotherapy effectively inhibits tumor progression. This presents WSB1 and its signaling network as potential therapeutic targets for a broad range of patients with cervical cancer.

Pituitary tumor-transforming gene-1 (PTTG1), one type of DNA repair-related gene, has been reported to be dysregulated in several tumors and serve as a tumor promotor. Previously, the oncogenic roles of PTTG1 were also reported in lung adenocarcinoma (LUAD). However, the prognostic values of PTTG1 in LUAD and the possible mechanism of its dysregulation have not been clarified. We analyzed TCGA datasets and reported that PTTG1 expression showed a distinct increase within LUAD specimens in comparison with nontumor specimens. Further survival study revealed that patients containing a great PTTG1 level had noticeably less overall survival and progression-free survival as compared with patients containing a low PTTG1 level. Multivariate analyses confirmed that PTTG1 expression was a factor of prognosis that is independent in terms of LUAD patients. Besides, PTTG1 methylation had a negative regulation on PTTG1, so PTTG1 had a high expressing level in LUAD tissues. However, the relation between hypermethylation and overall survival was not demonstrated using TCGA datasets. In addition, we observed that LUAD specimens with advanced stages exhibited a higher level of PTTG1. Finally, the dysregulated genes related to PTTG1 expression were screened, and KEGG assays revealed that the above genes were involved in the p53 signaling pathway, indicating the possible regulatory function of PTTG1 in the p53 signaling pathway. Overall, our findings suggest that PTTG1 may serve as an efficient clinical biomarker and a therapeutic target for patients suffering from LUAD.

Background: Activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) is differentially expressed in several tumor types. However, its association with immune cell infiltration remains elusive. Methods: AHSA1 expression was analyzed using The Cancer Genome Atlas (TCGA) pan-cancer data and normal tissue expression data from Genotype-Tissue Expression (GTEx). The clinical prognostic role of AHSA1 in pan-cancer was investigated, and an enrichment analysis of AHSA1 was performed using the R package “clusterProfiler.” We downloaded data regarding the immune cell infiltration level of TCGA pan-cancer tissues and analyzed the association between immune cell infiltration and AHSA1 expression. Results: The results of TCGA pan-cancer data analysis revealed that AHSA1 was overexpressed and associated with poor survival in patients with cancer. Furthermore, the infiltration levels of tumor-associated macrophages (TAMs) were higher, while those of CD8+ T cells were lower, in the high AHSA1 expression group. Conclusions: Our study suggests that AHSA1 is an oncogene and a risk factor for patient survival in cancer. AHSA1 may contribute to high infiltration levels of TAMs and low infiltration levels of CD8+ T cells, thus indicating that high AHSA1 expression may be associated with the tumor immunosuppressive microenvironment.

Changes in mitochondrial morphology by dysregulated mitochondrial fission-fusion proteins have been increasingly recognized as a hallmark of cancer. MiD49 (mitochondrial dynamics protein of 49 kDa) is a newly identified mitochondrial fission protein involved in the dynamic regulation of mitochondrial morphology. However, the expression pattern and biological functions of MiD49 in human cancers remain largely unexplored, especially in pancreatic cancer (PC). In the present study, the expression and clinical significance of MiD49 was firstly determined by RT-qPCR and western blot analyses in PC cell lines and tumor tissues. In addition, the biologic functions of MiD49 in PC cell growth and metastasis were investigated using gain- and loss-of-function assays both in vitro and in vivo. Moreover, the underlying mechanisms by which MiD49 regulates PC cell growth and metastasis were further explored. Our results showed that MiD49 was markedly downregulated in both PC cell lines and human PC specimens. Forced expression of MiD49 suppressed PC cell growth and metastasis both in vitro and in vivo, while knockdown of MiD49 exhibited the opposite effect. Mechanistic exploration demonstrated that the tumor-suppressive effect of MiD49 was mediated by decreased mitochondrial fission and subsequent reduced ROS production in PC cells. Our findings suggest a critical tumor-suppressive role played by MiD49 in pancreatic cancer.

Objectives: The mostly-resolved first wave of the COVID-19 epidemic in China provided a unique opportunity to investigate how the initial characteristics of the COVID-19 outbreak predict its subsequent magnitude. Methods: We collected publicly available COVID-19 epidemiological data from 436 Chinese cities from 16th January–15th March 2020. Based on 45 cities that reported >100 confirmed cases, we examined the correlation between early-stage epidemic characteristics and subsequent epidemic magnitude. Results: We identified a transition point from a slow- to a fast-growing phase for COVID-19 at 5.5 (95% CI, 4.6–6.4) days after the first report, and 30 confirmed cases marked a critical threshold for this transition. The average time for the number of confirmed cases to increase from 30 to 100 (time from 30-to-100) was 6.6 (5.3–7.9) days, and the average case-fatality rate in the first 100 confirmed cases (CFR-100) was 0.8% (0.2–1.4%). The subsequent epidemic size per million population was significantly associated with both of these indicators. We predicted a ranking of epidemic size in the cities based on these two indicators and found it highly correlated with the actual classification of epidemic size. Conclusions: Early epidemic characteristics are important indicators for the size of the entire epidemic.

Background Mitochondrial shape is dynamically changed by fusion and fission processes in cells, and dysfunction of this process has become one of the emerging hallmarks of cancer. However, the expression patterns and biological effects of mitochondrial fission and fusion proteins in pancreatic cancer (PC) are still unclear. Methods The expressions of mitochondrial fission and fusion proteins were first evaluated by quantitative reverse transcription polymerase chain reaction and western blot analysis in both PC cell lines and tissue samples. In addition, the biologic functions of the differentially expressed proteins in PC cell growth and metastasis both in vitro and in vivo and their potential underlying mechanisms were systematically explored. Results We first found that DRP1 was substantially upregulated in PC cell lines and tissue samples mainly due to the downregulation of miR-29a, which contributed to the poor survival of PC patients. DRP1 promoted the growth and metastasis of PC cells both in vitro and in vivo by inducing G1-S cell cycle transition and matrix metalloproteinase 2 secretion. Mechanistic investigations revealed that increased DRP1 upregulation-mediated mitochondrial fission and subsequently enhanced aerobic glycolysis were involved in the promotion of growth and metastasis by DRP1 in PC cells. Conclusions Our findings demonstrate that mitochondrial fusion protein DRP1 plays a critical oncogenic role in PC cells by enhancing aerobic glycolysis, which could serve as a novel therapeutic target for PC treatment.

A growing body of evidence has suggested that microRNAs (miRNAs) play a pivotal role in the development and progression of pancreatic cancer. miRNA-449a (miR-449a) has attracted particular interest due to its critical role in regulating cancer biology in numerous cancer types. However, whether miR-449a is involved in the regulation of pancreatic cancer development and progression remains unknown. In this study, we aimed to investigate the expression pattern and potential biological function of miR-449a in pancreatic cancer. Our results showed that miR-449a levels were significantly down-regulated in pancreatic cancer tissues and cell lines. The overexpression of miR-449a significantly inhibited the proliferation and invasion of pancreatic cancer cells, whereas miR-449a inhibition promoted the proliferation and invasion of pancreatic cancer cells. Bioinformatic analysis predicted that ataxia-telangiectasia group D complementing gene (ATDC) was a potential target gene of miR-449a. The dual-luciferase reporter assay revealed that miR-449a directly binds to the 3'-untranslated region of ATDC. Further analysis demonstrated that miR-449a negatively controls the mRNA and protein expression of ATDC in pancreatic cancer cells. In addition, an inverse correlation between miR-449a and ATDC expression was observed in clinical tissues. Notably, the overexpression of ATDC partially reversed the antitumor effect of miR-449a overexpression, while the silencing of ATDC abrogated the oncogenic effect of miR-449a inhibition in pancreatic cancer cells. In addition, the overexpression of miR-449a inhibited the accumulation of β-catenin and blocked the activation of Wnt signaling by targeting ATDC. Taken together, our study reveals a tumor suppressive role of miR-449a in pancreatic cancer, and demonstrates that the antitumor role of miR-449a is associated with its regulatory effect on ATDC expression. Our study suggests that the miR-449a/ATDC axis may play an important role in the development and progression of pancreatic cancer and may provide potential targets for the development of cancer therapies.

Background and objective The expression of long noncoding RNA HOX antisense RNA (HO-TAIR) is abnormal in a variety of tumors. The aim of this study is to explore the serum levels and clinical significance of HOTAIR in patients with non-small cell lung cancer (NSCLC). Methods The serum levels of HOTAIR were detected by real-time quantitative polymerase chain reaction (PCR) in 64 NSCLC patients and 64 normal controls. The rela-tionships between the serum levels of HOTAIR and clinical pathological parameters were analyzed. Results Compared with normal controls, the serum levels of HOTAIR in patients with NSCLC increased significantly (P<0.01). The serum levels of HOTAIR were correlated with tumor size, tumor-node-metastasis (TNM) stage and lymph node me-tastasis (P<0.05), but not with age, gender, smoking, differentiation and histology (P>0.05). Conclusion The serum levels of HOTAIR in patients with NSCLC are significantly higher, and HOTAIR may be involved in the pathogenesis of NSCLC.