Improving the effects of radiotherapy, such as heavy ion radiation, is currently a research priority for oncotherapy. Long non-coding RNAs (lncRNAs) are a subtype of noncoding RNAs involved in the therapeutic response to tumor radiotherapy. However, little is known about the variations in lncRNAs that occur after heavy ion radiation therapy. In this study, we established two kinds of Agilent Human lncRNA arrays and examined the effects of heavy ion radiation and X-ray irradiation on HeLa cells. We compared the differences in lncRNA expression (>=2-fold changes) between cells treated with the two types of radiation and control cells and identified 504 lncRNAs and 285 mRNAs that were differentially expressed. Among these lncRNAs, TCONS-00009910 was the most highly up-regulated lncRNA, while NONHSAT060631 was the most down-regulated lncRNA in both groups. To validate these sequencing data, RT-PCR was performed, and similar findings were obtained. GO and KEGG pathway analyses were employed to probe the potential functions of the affected lncRNAs. Numerous lncRNAs were changed after radiation exposure, showing that they may have important functions in the response to tumour radiotherapy. The present findings may help to elucidate the mechanism by which lncRNAs affect the clinical responses of cancer to radiation and may provide potential diagnostic and therapeutic targets for cancer therapy.

Background: Pancreatic cancer is one of the most aggressive malignancies globally, with no improvement in the cure rates yet.Caveolin-2 (CAV2) has been repeatedly reported to play an important role in cellular transport and signalling and in exhibiting a pro-oncogenic response in a variety of tumours, although its specific action mechanisms in pancreatic cancer are not well documented. MiRNA is recognized as a therapeutic target for a variety of tumours, making it an important regulator of the Wnt/β-catenin signalling pathway. MiR-4723/Wnt7A constitutes an oncogenic signalling axis in pancreatic cancer by targeting and inhibiting Wnt7A through the activation of MiR4723, but its molecular action mechanism remains unexplored. Therefore, in the present study, we investigated the effect of CAV2 on the MiR-4723/Wnt7A pathway and its action mechanism. Methods: We employed TCGA, the GEO database for bioinformatics analysis, cell proliferation assay, wound healing assay, Transwell assay, colony-forming assay, qRT-PCR, and Western blotting to validate the cancer-promoting role of CAV2 in pancreatic cancer and to determine its potential target WNT7A. We then explored CAV2 as a positive regulator of the Wnt7A/β-catenin pathway through immunofluorescence assay, qRT-PCR, and Western blotting. Database analyses, CCK-8 and qRT-PCR revealed that MiR-4723 is an oncogene in pancreatic cancer. Luciferase assay and qRT-PCR revealed that MiR-4723 is a negative regulator of the Wnt7A/β-catenin pathway. To investigate the mechanism of CAV2 action on MiR-4723/Wnt7A, we detected the gene expression of CAV2 through qRT-PCR after MiR-4723 overexpression. Several genes related to endocytosis and epithelial-mesenchymal transition (EMT) were subsequently analysed through immunofluorescence, Western blotting, and qRT-PCR. Results: Overexpression of CAV2 promotes invasion, migration, cloning and metastasis of pancreatic cancer cells. Overexpression of MiR-4723 inhibits CAV2 expression. Here, we are the first to demonstrate that CAV2 exerts a pro-carcinogenic effect on pancreatic cancer through the activation of the Wnt7A/β-catenin signalling pathway. Conclusion: CAV2 can regulate the MiR-4723/Wnt7A signalling axis in pancreatic cancer cell lines by inhibiting endocytosis and promoting EMT, thereby fulfilling the mechanism pro-carcinogenic effects.

FOXD1 has been reported to function as an oncogene in several types of cancer. This study evaluated the expression of FOXD1 and its role in head and neck squamous cell carcinoma (HNSCC). We mined the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases for expression profiles, clinical significance, and potential mechanisms of FOXD1in HNSCC. Our validation cohort consisted of FOXD1 mRNA expression in 162 paired HNSCC and adjacent normal tissues, as determined using quantitative real-time polymerase chain reaction. FOXD1 expression was upregulated in HNSCC in the public databases and in the validation cohort. The expression level of FOXD1 was associated with DNA amplification and methylation level. The areas under the curves (AUC) of TCGA cohort and the validation cohort were 0.855 and 0.843, respectively. Furthermore, higher FOXD1 expression was significantly associated with worse overall survival (hazard ratio [HR]: 1.849, 95% confidence interval [CI]: 1.280-2.670, P = 0.001) and a lower rate of recurrence-free survival (HR: 1.650, 95% CI: 1.058-2.575, P = 0.027) in patients with HNSCC. Moreover, gene set enrichment analysis showed that cases of HNSCC with FOXD1 overexpression were enriched in bladder cancer, cell cycle, DNA replication, glycosaminoglycan biosynthesis chondroitin sulfate, homologous recombination, glycan biosynthesis, nucleotide excision repair, p53 signaling pathway, pyrimidine metabolism, and spliceosome pathways. In summary, FOXD1 was significantly upregulated in HNSCC and was a good diagnostic biomarker and an independent predictor of poor survival and low rate of recurrence-free survival in patients with HNSCC.

Background: Although it is widely accepted that invasive micropapillary carcinoma (IMPC) presents more aggressive behavior and has a higher aggressive behavior, the prognosis of IMPC compared with invasive ductal carcinoma (IDC) remains controversial. We conducted this study to explore gene expression profiles of IMPC and establish a competing nomogram that predicts the survival outcomes across these two groups of patients. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed. Propensity score matching (PSM) was used to adjust for potential baseline confounding between IMPC and IDC group. The Kaplan-Meier method was used to calculate the occurrence of overall mortality. The Gray method was used to estimate the rate of breast cancer specific death (BCSD). A competing regression model was used to evaluate factors associated with BCSD. A nomogram based on the competing risk regression model was established to predict individual outcomes. IMPC-specific gene expression profiles were explored using microarrays data from the Gene Expression Omnibus (GEO) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. Results: In this study, 330786 (99.62%) patients with IDC 1247 (0.38%) patients with IMPC were included. Patients with IMPC had more lymph node involvement and a larger tumor size compared with those with IDC. After PSM, many distributional differences were eliminated, showing that the IMPC and IDC group were more similar. Patients with IMPC had a favorable prognosis with statistical significance compared with patients with IDC (overall mortality HR = 0.68; 95%CI, 0.53-0.86; P = 0.002). Based on Gray method, patients with IMPC had a favorable prognosis with significant statistical significance compared with patients with IDC (BCSD SHR = 0.64; 95%CI, 0.47-0.88; P = 0.006). Multivariate analysis based on competing risk model demonstrated that IMPC was a favorable independent factor for BCSD. The nomogram could accurately predict BCSD with a high internal and external validated C-index (0.835, 0.818 respectively). A total of 53 upregulated differentially expressed genes (DEGs) and 40 downregulated DEGs of IMPC was identified. The GO analysis results showed that downregulated DEGs were significantly enriched in extracellular structure organization, extracellular matrix, cell-substrate adhesion junction. KEGG analysis of selective gene sets shows that downregulated DEGs significantly enriched for processes related to carbon metabolism, Rap1 signaling pathway. Conclusion: In the current study, IMPC accounted for 0.38% of the entire cohort. IMPC was found to be a favorable independent prognostic factor. The present study identified gene expression profiles and signal pathways of IMPC. The developed nomogram can help the oncologists to predict individual outcomes more accurately.

Liver cancer is one of the leading cancers, especially in developing countries. Understanding the biomechanical properties of the liver cancer cells can not only help to elucidate the mechanisms behind the cancer progression, but also provide important information for diagnosis and treatment. At the cellular level, we used well-established atomic force microscopy (AFM) techniques to characterize the heterogeneity of mechanical properties of two different types of human liver cancer cells and a normal liver cell line. Stiffness maps with a resolution of 128x128 were acquired for each cell. The distributions of the indentation moduli of the cells showed significant differences between cancerous cells and healthy controls. Significantly, the variability was even greater amongst different types of cancerous cells. Fitting of the histogram of the effective moduli using a normal distribution function showed the Bel7402 cells were stiffer than the normal cells while HepG2 cells were softer. Morphological analysis of the cell structures also showed a higher cytoskeleton content among the cancerous cells. Results provided a foundation for applying knowledge of cell stiffness heterogeneity to search for tissue-level, early-stage indicators of liver cancer.

Background: The mechanism underlying cisplatin resistance in colorectal carcinoma (CRC) has not yet been elucidated. This study is aimed to illustrate the indispensable role of proline-rich acidic protein 1 (PRAP1) in cisplatin-resistant CRC. Methods: Cell viability and apoptosis were monitored using cell counting kit-8 and flow cytometry. Immunofluorescence and morphological analysis were used to determine mitotic arrest in cells. In vivo drug resistance was evaluated using a tumor xenograft assay. Results: PRAP1 was highly expressed in cisplatin-resistant CRC. PRAP1-upregulation in HCT-116 cells increased chemoresistance to cisplatin, whereas RNAi-mediated knockdown of PRAP1 sensitized cisplatin-resistant HCT-116 cells (HCT-116/DDP) to cisplatin. PRAP1-upregulation in HCT-116 cells hindered mitotic arrest and the formation of mitotic checkpoint complexes (MCC), followed by an increase in multidrug-resistant proteins such as p-glycoprotein 1 and multidrug resistance-associated protein 1, while PRAP1-knockdown in HCT-116/DDP cells partly restored colcemid-induced mitotic arrest and MCC assembly, resulting in decreased multidrug-resistant protein levels. PRAP1 downregulation-mediated sensitization to cisplatin in HCT-116/DDP cells was abolished by the inhibition of mitotic kinase activity by limiting MCC assembly. Additionally, PRAP1-upregulation increased cisplatin-resistance in CRC in vivo. Mechanistically, PRAP1 increased the expression of mitotic arrest deficient 1 (MAD1), that competitively binds to mitotic arrest deficient 2 (MAD2) in cisplatin-resistant CRC cells, leading to failed assembly of MCC and subsequent chemotherapy resistance. Conclusion: PRAP1-overexpression caused cisplatin resistance in CRC. Possibly, PRAP1 induced an increase in MAD1, which competitively interacted with MAD2 and subsequently restrained the formation of MCC, resulting in CRC cells escape from the supervision of MCC and chemotherapy resistance.

Cancer cells usually utilize glucose as a carbon source for aerobic glycolysis, a phenomenon known as the Warburg effect. And a high rate of glycolysis has been observed in lung cancer cells. The growing evidence indicates that long non-coding RNAs (lncRNAs) are important players in lung cancer initiation and progression. However, the correlation between lncRNAs and glycolysis remains unclear. In this study, we recognized a lncRNA, LNC CRYBG3, which can interact with lactate dehydrogenase A (LDHA), a vital enzyme of glycolysis, is highly upregulated in both clinical lung cancer tissues and in vitro cultured lung cancer cell lines. A positive correlation between the expression level of LNC CRYBG3 and LDHA expression levels is observed. In another hand, LNC CRYBG3 is a regulator of glycolysis and its overexpression promoted the uptake of glucose and the production of lactate whereas the knockdown of LNC CRYBG3 led to opposite results and suppressed cell proliferation. These results indicated that LNC CRYBG3 might be a novel target for lung cancer treatment.

Background: Small cell lung cancer (SCLC) is the most malignant type of lung cancer characterized by rapid progression, early metastasis and recurrence. In recent years, circulating tumor cells (CTCs) were found to play an important role in tumor invasion, metastasis, recurrence and prognosis. Methods: CTCs were detected in 138 patients with newly diagnosed SCLC from January 2012 to December 2018. Nomogram prediction models were constructed based on prognostic factors screened by multivariate Cox regression analysis and the risk stratification of SCLC patients were performed on basis of nomogram points. A total of 108 patients from January 2012 to December 2016 were assigned to a training group, and 30 patients from January 2017 to December 2018 were included into the validation group for nomogram analysis. This study was approved by ethics committee of Guangzhou First People's Hospital and all subjects provided informed consent. Results: The number of CTCs was associated with age, lymph node metastasis (N), distant metastasis (M), TNM staging, and NSE. The high number of CTC predicted adverse prognosis, and the AUC of time-dependent ROC curve was all high than 0.5. In the training group, after multivariate COX regression screening, the factors in the median survival time (MST) and overall survival (OS) nomogram prediction models were age, TNM, CTC, NSE and treatment mode. The C-index of the nomograms in internal validation for MST and OS was 0.813 and in external validation for MST and OS were 0.885. The AUC of ROC curves for nomogram were high than 0.5. Finally, risk stratification could be effectively performed on the basis of nomogram points. Conclusions: CTC can be served as a predictive and prognostic factor for SCLC, and the nomogram models constructed by CTC and multiple clinical parameters can comprehensively predict the prognosis of SCLC patients and perform risk stratification.

The number of reported young breast cancer cases has increased dramatically recently. The impact of age on the outcomes of breast cancers remains controversial. Our study aimed to explore the factors that can stratify the impact of young age on the prognosis of early breast cancer patients. In total, 244,324 patients with early breast cancer in the Surveillance, Epidemiology, and End Results database were identified from 1990 to 2007. Survival curves were generated using the Kaplan-Meier method. The 5- and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Multivariable analyses were used to identify prognosti c variables (without age) to construct the nomograms. The risk score developed from the nomogram was used to classify the cohort into three subgroups (low-, medium- and high-risk subgroup). Approximately 8.89% of women were diagnosed with breast cancer at a young age (≤ 40 years). Clinical nomogram had the potential ability to predict CSS accurately with a well C-index (0.785). Subgroup analysis indicated that the risk score as the sole factor can stratify the impact of young age on the prognosis of early breast cancer patients. Young breast cancer patients had a worse prognosis in the low-risk (HR=0.61; 95% CI: 0.57-0.65; P<0.001) or medium-risk subgroup (HR=0.89; 95% CI: 0.85-0.93; P<0.01) than in the high-risk subgroup (P=0.431). In conclusion, the worse prognosis of young women only appeared in the low- and medium-risk subgroups rather than in the high-risk subgroup. The risk score yielded from the nomogram model can assist clinical decision making for young breast cancer patients.

Long noncoding RNAs (lncRNAs) are usually associated with tumor development and progression and some of them are dysregulated in various human cancers. The mechanisms underlying their dysregulation are worth further study. Here, we demonstrate that the expression level of LNC CRYBG3 is correlated with 1501 aberrantly expressed proteins in A549 cells (non-small cell lung cancer (NSCLC) cells). LNC CRYBG3 overexpression results in M phase arrest and promoted cell death, whereas LNC CRYBG3 knockdown did not elicit the opposite effects. The overexpression of LNC CRYBG3 inhibits cell proliferation both in vitro and in vivo. Moreover, it upregulates the expression of cyclin B1 and the phosphorylation of H3, whereas it inhibited the expression of cyclin-dependent kinase 6 and cyclin D1. Taken together, these findings suggest that LNC CRYBG3 regulates the cell cycle process of A549 cells, suggesting its potential application for the treatment of this disease.

MicroRNAs (miRNAs) play important roles in the regulation of cellular stress responses. We previously uncovered 10 novel human miRNAs which are induced by X-ray irradiation in HeLa cells using Solexa deep sequencing. The most highly expressed new miRNA, miR-5094, was predicted to target STAT5b. This study wonders whether miR-5094 participates in cellular radiation response via STAT5b. Firstly, direct interaction between miRNA-5094 and the STAT5b 3'-UTR was confirmed by luciferase reporter assay. Then, the radiation responsive expression of miR-5094 and STAT5b were measured in HeLa and Jurkat cells, and the expressions of down-stream genes of STAT5b after ionizing radiation (IR) were detected in HeLa cells. At last, the effects of miR-5094 on survival fraction, cell proliferation, cell cycle arrest and apoptosis induced by IR were investigated in HeLa cells, Jurkat cells and human peripheral blood T cells. It was found that up-regulation of miR-5094 by radiation induction or miRNA mimic transfection suppressed expression of STAT5b, and consequently decreased the transcription of down-stream Igf-1 and Bcl-2. Additionally, over expression of miR-5094 resulted in proliferation suppression and knockdown of miR-5094 by miRNA inhibitor after irradiation partially reversed the proliferation suppression induced by miR-5094 in HeLa cells, Jurkat cells and CD4+ T cells. Collectively, our findings demonstrate that up-regulation of miR-5094 down-regulated the expression of STAT5b, thereby suppressing cell proliferation after X-ray irradiation.