Long non-coding RNA PRNCR1 has an oncogenic role in breast cancer.

Long non-coding RNAs (lncRNAs) have important roles in the development and progression of various types of human cancer. However, the expression and function of the lncRNA prostate cancer-associated non-coding RNA 1 (PRNCR1) in breast cancer remains unclear. Reverse transcription-quantitative PCR was performed to measure the levels of mRNA expression. Cell counting kit-8, flow cytometry, wound healing and Transwell assays were also performed to study cell proliferation, cell cycle, migration and invasion, respectively. The results of the present study revealed that PRNCR1 expression levels were higher in breast cancer tissues compared with adjacent normal tissues in a patient study. It was also determined that high expression of PRNCR1 was significantly associated with advanced clinical stage, positive metastasis and poor prognosis for patients with breast cancer. In vitro experiments determined that PRNCR1 was significantly upregulated in the breast cancer cell lines BT-549, MCF-7, SK-BR-3 and MDA-MB-231 compared with the normal human breast cell line, MCF-10A. Silencing of PRNCR1 significantly inhibited the proliferation, colony formation, cell cycle progression, migration and invasion of SK-BR-3 and BT-549 cells, while cell apoptosis was induced. In addition, knockdown of PRNCR1 suppressed epithelial-mesenchymal transition in SK-BR-3 and BT-549 cells. In summary, the present results demonstrated that lncRNA PRNCR1 was significantly upregulated in breast cancer and was associated with cancer progression and poor patient prognosis. In vitro experiments determined that knockdown of PRNCR1 inhibited the malignant phenotypes of breast cancer cells. Taken together, the results indicated that PRNCR1 may be used as a potential therapeutic target for patients with breast cancer.

TNF receptor-associated factor 1 as a biomarker for assessment of non-small cell lung cancer metastasis and overall survival.

BACKGROUND AND AIM: Non-small cell lung cancer (NSCLC), which comprises 80%-85% of all lung cancer cases, is one of the most common human malignancies. Despite great improvements in diagnostic technology and the introduction of new therapeutic agents in recent years, the 5-year survival rate of NSCLC is still low. Tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) plays an important role in the TNF-related apoptosis-inducing ligand (TRAIL) associated signal pathway. METHODS: In this study, we aim to illuminate the function of TRAF1 in NSCLC. Toward that end, TRAF1 expression was detected using immunohistochemistry (IHC) in specimens from 200 NSCLC patients. The function of TRAF1 in the A549 and H1299 cell lines was evaluated by colony formation and MTT assays. RESULTS: Our data showed that TRAF1 was significantly upregulated in NSCLC tissues. TRAF1 expression was positively associated with NSCLC lymphatic metastasis and clinical stage and was negatively associated with overall patient survival. TRAF1 promoted NSCLC cell proliferation CONCLUSION: TRAF1 expression was positively associated with NSCLC lymphatic metastasis and histological grade and was negatively associated with overall patient survival. TRAF1 may be an important therapeutic target for NSCLC.

miRNAs in acute myeloid leukemia.

MicroRNAs (miRNAs) are small, non-coding RNAs found throughout the eukaryotes that control the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells and tumorigenesis. Widespread dysregulation of miRNAs have been found in hematological malignancies, including human acute myeloid leukemia (AML). A comprehensive understanding of the role of miRNAs within the complex regulatory networks that are disrupted in malignant AML cells is a prerequisite for the development of therapeutic strategies employing miRNA modulators. Herein, we review the roles of emerging miRNAs and the miRNAs regulatory networks in AML pathogenesis, prognosis, and miRNA-directed therapies.

Pathway Analysis Based on Attractor and Cross Talk in Colon Cancer.

Colon cancer is the third and second most common cancer form in men and women worldwide. It is generally accepted that colon cancer mainly results from diet. The aim of this study was to identify core pathways which elucidated the molecular mechanisms in colon cancer. The microarray data of E-GEOD-44861 was downloaded from ArrayExpress database. All human pathways were obtained from Kyoto Encyclopedia of Genes and Genomes database. In total, 135 differential expressed genes (DEG) were identified using Linear Models for Microarray Data package. Differential pathways were identified with the method of attractor after overlapping with DEG. Pathway cross talk network (PCN) was constructed by combining protein-protein interactions and differential pathways. Cross talks of all pathways were obtained in PCN. There were 65 pathways with RankProd (RP) values < 0.05 and 16 pathways with Impact Factors (IF) values > 100. Five pathways were satisfied with P value < 0.05, RP values < 0.05, and IF values > 100, which were considered to be the most important pathways in colon cancer. In conclusion, the five pathways were identified in the center status of colon cancer, which may contribute to understanding the mechanism and development of colon cancer.

Enhancing the treatment effect on melanoma by heat shock protein 70-peptide complexes purified from human melanoma cell lines.

Dendritic cell (DC) vaccines are currently one of the most effective approaches to treat melanoma. The immunogenicity of antigens loaded into DCs determines the treatment effects. Patients treated with autologous antigen-loaded DC vaccines achieve the best therapeutic effects. In China, most melanoma patients cannot access their autologous antigens because of formalin treatment of tumor tissue after surgery. In the present study, we purified heat shock protein 70 (HSP70)-peptide complexes (PCs) from human melanoma cell lines A375, A875, M21, M14, WM­35, and SK­HEL­1. We named the purified product as M­HSP70­PCs, and determined its immunological activities. Autologous HSP70­PCs purified from primary tumor cells of melanoma patients (nine cases) were used as controls. These two kinds of tumor antigenic complexes loaded into DCs were used to stimulate an antitumor response against tumor cells in the corresponding patients. Mature DCs pulsed with M­HSP70­PCs stimulated autologous T cells to secrete the same levels of type I cytokines compared with the autologous HSP70­PCs. Moreover, DCs pulsed with M­HSP70­PCs induced CD8+ T cells with an equal ability to kill melanoma cells from patients compared with autologous HSP70­PCs. Next, we used these PC­pulsed autologous DCs and induced autologous specific CD8+ T cells to treat one patient with melanoma of the nasal skin and lung metastasis. The treatment achieved a good effect after six cycles. These findings provide a new direction for DC-based immunotherapy for melanoma patients who cannot access autologous antigens.

[Construction of Fat-1 eukaryotic expression vector of excision markers and the establishment of transgenic sheep cell lines].

In order to establish marker-free transgenic cell lines, we cloned Fat-1 gene, attB and Loxp sequences by PCR. Then we inserted these sequences to pN1-EGFP vector and got pEGFP-N1-Fat-1 expression vector. PhiC31 integrase mRNA which was generated by in vitro transcription and a pEGFP-N1-Fat-1 expression vector co-electroporated into sheep fetal fibroblasts, and then we got transgenic cell lines expressing green fluorescence. Prokaryotic expression and purification of Cre recombinant protein was performed. Cre recombinant protein was transducted into stably-transfected cell colonies. We identified cell colonies by sequencing and established marker-free transgenic cell lines and eventually- established marker-free transgenic cell lines which were building more safely basic for producing Fat-1 transgenic animals.

The progress of angiogenic factors in the development of leukemias.

Angiogenic factors have been demonstrated to play important roles in modulating angiogenesis of solid tumors. Recently, accumulating studies extensively indicated that some angiogenic factors widely exist in malignant cells of hematologic malignancy, which regulated the expression of a number of genes that were involved in abnormal proliferation, differentiation and apoptosis of these cells. With deep research of angiogenic factors, its expression, function and regulatory mechanism were gradually elucidated, and some of them were related to the development and prognosis of leukemia, or provide more possible strategies for treatment of patients with leukemia. Herein, we summarize the progress in study of some important angiogenic factors and hematological malignancies.