Role of Exosomal Non-Coding RNA in the Tumour Microenvironment of Genitourinary System Tumours.

In recent years, genitourinary system tumors are common in people of all ages, seriously affecting the quality of life of patients, the pathogenesis and treatment of these diseases are constantly being updated and improved. Exosomes, with a lipid bilayer that enable delivery of their contents into body fluids or other cells. Exosomes can regulate the tumor microenvironment, and play an important role in tumor development. In turn, cellular and non-cellular components of tumor microenvironment also affect the occurrence, progression, invasion and metastasis of tumor. Non-coding RNAs have been shown to be able to be ingested and released by exosomes, and are seen as a potential tool in cancer diagnosis and treatment. Here, we summarize the effect of non-coding RNAs of exosome contents on the tumor microenvironment of genitourinary system tumor, expound the significance of non-coding RNAs of exosome in the occurrence, development, diagnosis and treatment of cancers.

Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

LMP1 stimulates the transcription of eIF4E to promote the proliferation, migration and invasion of human nasopharyngeal carcinoma.

Eukaryotic translation initiation factor 4E (eIF4E) is the rate-limiting translation initiation factor for many oncogenes. Previous studies have shown eIF4E overexpression in nasopharyngeal carcinoma (NPC). We aimed to study whether viral oncogene latent membrane protein 1 (LMP1) stimulates the transcription of eIF4E to promote NPC malignancy. In NPC cell lines (CNE1 and CNE2), ectopic LMP1 significantly increased the mRNA and protein levels of eIF4E and the transcriptional activity of the eIF4E promoter in a LMP1-plasmid-transfected dose-dependent manner. As a backward experiment, knocking down of LMP1 significantly reduced eIF4E mRNA in B95-8 cells. In the high LMP1 expression condition, knocking down of c-Myc significantly reduced eIF4E mRNA in both NPC and B95-8 cells, and knocking down of eIF4E significantly inhibited the tumor proliferation, migration and invasion promoted by LMP1. The results indicated that LMP1 stimulates the transcription of eIF4E via c-Myc to promote NPC. To the best of our knowledge, this is the first evidence that LMP1 stimulates the transcription of eIF4E. This might be an important cause of the overexpression of eIF4E in NPC and be the novel mechanism by which LMP1 initiates cancer. LMP1-stimulated eIF4E initiates the translation of those oncogenes transcriptionally activated by LMP1 to amplify and pass down the carcinogenesis signals launched by LMP1.

Heparanase overexpression participates in tumor growth of cervical cancer in vitro and in vivo.

Expression of heparanase is associated with invasion, metastasis and angiogenesis of a variety of human cancers. However, the roles of heparanase in cervical cancer are not clear. The aim of this study is to determine whether up-regulation of heparanase expression can promote growth of cervical cancer in vitro and in vivo. Heparanase protein expression was analyzed in cervical cancer patients using immunohistochemistry. In addition, expression of heparanase was also examined in cervical cancer cell lines. A series of in vivo and in vitro assays was performed to elucidate the role of heparanase in tumor growth of cervical cancer. Positive rate of heparanase was 63.3 % (38/60) in cervical cancer patients by immunohistochemistry, and it was significantly correlated with tumor size and clinical stage (P < 0.05). Overexpression of heparanase inhibited apoptosis of cervical cancer cells. Moreover, ectopic overexpression of heparanase in cervical cancer cells promoted proliferation of cervical cancer cells in vitro and tumor growth in vivo. These results suggest that heparanase participates in tumor growth of cervical cancer by influencing the proliferation and apoptosis of cervical cancer cells, and heparanase could be used as an effective therapeutic target for cervical cancer.

[Expression and clinical significance of nm23-H1, Fas and FasL in colorectal carcinoma tissues].

OBJECTIVE: To investigate the expression and clinical significance of nm23-H1, Fas and FasL in colorectal carcinoma tissues. METHODS: The expression levels of nm23-H1, Fas and FasL in 48 cases of colorectal carcinoma tissues and 15 cases of normal colorectal tissues were determined by SP immunohistochemical staining. RESULTS: Positive expression rates of nm23-H1, Fas and FasL in colorectal carcinoma were (25.0 +/- 2.6)%, (41.7 +/- 2.7) and (77.1 +/- 2.7)% respectively; the positive expression rates of nm23-H1 and Fas were lower than that in the normal colorectal tissues (P<0.01); the FasL expression rate in colorectal carcinoma tissues was higher than that in the normal colorectal tissues (P<0.01); the lower expression of nm23-H1 and Fas, and the higher expression of FasL in colorectal carcinoma were correlated with the type of carcinoma histology, lymph node metastasis, Dukes' stage and prognosis (P<0.01). CONCLUSION: These results suggest that the lower expression of nm23-H1 and Fas and higher expression of FasL may be used as a good indicator in evaluating lymph node metastasis and prognosis.