E6E7 regulates the HK2 expression in cervical cancer via GSK3ß/FTO signal.

BACKGROUND: Cervical cancer is one of the most common cancers in women worldwide. Hexokinase 2 (HK2) is responsible for phosphorylating glucose into glucose-6-phosphate, which is required for tumorigenesis and metastasis. METHODS: E6E7 and FTO were exogenously expressed, and their effects on HK2 mRNA and protein levels were detected by RT-qPCR and Western blot. RESULTS: The exogenous expression of E6E7 in SiHa and C33A cells up-regulated the mRNA and protein levels of intracellular HK2, up-regulated the total m6A levels, changed the expression of m6A proteins and activated the GSK3ß transcription. The expression levels of METTL3 and WTAP were enhanced, whereas the expression of FTO and ALKBH5 were decreased. In addition, FTO down-regulated the mRNA and protein levels of HK2. FTO overexpression partially inhibited the up-regulated expression of HK2 caused by E6E7. Furthermore, FTO overexpression increased the level of HK2 pre-mRNA in the nucleus and decreased the level of mature HK2 mRNA in the cytoplasm. We also found that GSK3ß overexpression enhanced FTO ubiquitination and decreased FTO protein levels. CONCLUSION: This study found that E6E7 oncogene activates the transcription of GSK3ß; GSK3ß can promote the ubiquitination-proteasomal degradation of FTO and reduce the level of FTO protein; FTO inhibits the maturation and translation of HK2 mRNA by retaining HK2 pre-mRNA in the nucleus.

LINC01133 promotes the progression of cervical cancer by sponging miR-4784 to up-regulate AHDC1.

Cervical cancer, as the deadliest gynecological tumor with high risk of incidence, manifests aberrantly expressed lncRNAs in the malignant cellular processes. Long intergenic non-protein coding RNA 1133 (LINC01133) has been acknowledged to actively participate in aggressive tumor phenotypes. Our study focused on the identification of the function and corresponding mechanism of the novel molecule, LINC01133 in cervical cancer. LINC01133 expression profile was validated by digging The Cancer Genome Atlas (TCGA) database and qRT-PCR analysis. A considerably up-regulated expression of LINC01133 was unveiled. The results of CCK-8, trypan blue exclusion, EdU and transwell migration assays manifested the facilitating property of LINC01133 in cervical cancer. The epithelial-mesenchymal transition (EMT) was also exacerbated by LINCO1133. Apoptotic rate of cervical cancer cells was promoted after silencing LINCO1133. Mechanically, LINC01133 functioning as a ceRNA targeted miR-4784 to augment AHDC1 expression. Finally, LINCO1133/miR-4784 aggravated the malignant growth and aggressiveness and EMT of cervical cancer in an AHDC1-dependant way.

Serum level of DKK-1 and its prognostic potential in non-small cell lung cancer.

BACKGROUND: The aim of the present study was to measure the serum level of dickkopf-1(DKK-1) in patients with non-small cell lung cancer (NSCLC), and to determine the prognostic potential of serum DKK-1 in NSCLC. MATERIAL AND METHODS: The present study included a total of 150 patients with NSCLC and 150 healthy controls. Serum level of DKK-1 was measured by enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t-tests. Categorical variables were presented as rates and analyzed by using the chi-square test or Fisher's exact test. The overall survival was analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. RESULTS: We found that serum DKK-1 level was significantly higher in patients with NSCLC than healthy controls. Mean serum DKK-1 level was 31.42 ± 6.32 ng/ml in the NSCLC group and 14.12 ± 3.29 ng/ml in the healthy control group (p <0.01). Serum DKK-1 level expression level was significantly positively correlated with TNM stage (p = 0.009), lymph node involvement(p = 0.001), and distant metastases(p < 0.001).In the multivariate Cox proportional hazards analysis, high DKK-1 expression was independently associated with poor survival (P < 0.001; HR = 3.98; 95% CI =2.19-4.83). CONCLUSIONS: In conclusion, our results showed that DKK-1 was overexpressed in NSCLC, and DKK-1 in serum was a good predictor of poor prognosis in patients with NSCLC. More researches are needed in the future to clarify the detailed mechanism of DKK-1 in the carcinogenesis and metastasis of NSCLC. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1471414150119415.

miR-99a promotes proliferation targeting FGFR3 in human epithelial ovarian cancer cells.

MiRNAs have been reported as important regulators in normal physiological processes, human cancer, and even their roles as therapeutic targets have been proposed. In epithelial ovarian cancer (EOC), the expression of miRNAs is reported to remarkably deregulate, showing that miRNAs are involved in the initiation and progression of this disease. In this study, we found that miR-99a was obviously decreased in EOC tissues, serums and cell lines SKOV-3. Importantly, fibroblast growth factor receptor 3 (FGFR3), predicted to be one target gene of miR-99a using computational algorithms, was higher in expression in EOC cells. Subsequently, FGFR3 was proved to be direct target of miR-99a by dual luciferase assay. Furthermore, overexpression of miR-99a dramatically suppressed expression level of FGFR3 at both mRNA and protein levels, proving FGFR3 to be inversely correlated with miR-99a. Finally, overexpression of miR-99a could significantly inhibit EOC cell proliferation in vitro by decreasing the expression of FGFR3 which also reduced the EOC cell growth after siRNA knockdown. Conclusively, miR-99a expression was remarkably downregulated in serums, tissues and cell and suppresses EOC cell proliferation by targeting FGFR3, suggesting miR-99a as a prospective prognosis marker and potential tumor suppressor for EOC therapeutics.

[Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues].

AIM: The differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues was investigated. METHODS: Restriction fragment differential display polymerase chain reaction (RFDD-PCR), semi-quantitative RT-PCR and immunohistochemical staining were applied to analyze the differentially expressed genes and proteins of ubiquitin specific proteases (USPs), USP2 and USP14, and ubiquitin factor E4A (UBE4A) between ovarian serous cystadenocarcinoma and adjacent normal tissues obtained from 40 patients aged from 29 to 72 years old, collected in 2005 year at excision of surgical operation with ovarian serous cystadenocarcinoma. RESULTS: USP2, USP14 and UBE4A were over-expressed (>3 folds) in ovarian serous cystadenocarcinoma tissues compared to normal tissues. CONCLUSION: The results suggest that the activity of ubiquitin-proteasome system is obviously enhanced in ovarian cancer.