Overexpression of Ubiquilin4 is associated with poor prognosis in patients with cervical cancer.

BACKGROUND: Ubiquilins (UBQLNs) are important factors for cell proteostasis maintenance. UBQLNs are involved in the modulation of the cell cycle, as well as in apoptosis, membrane receptors regulation, DNA repair, epithelial-mesenchymal transition, and miRNA activities. They also affect the selection of double-strand break repair pathways. Abnormal UBQLNs expression can lead to many diseases, including cancer. Studies have found that the expression of Ubiquilin4 (UBQLN4) is associated with the development of several tumor types. However, the association between UBQLN4 and cervical cancer has not been examined yet. AIM: To investigate the expression of UBQLN4 in cervical cancer and to evaluate its correlation with disease prognosis. METHODS: Immunohistochemistry was performed to examine the expression of UBQLN4 in 117 cervical cancer tissues and 32 matching pericervical tissues. Paired t-test (two-tailed) was used to compare the differences between groups. We collected patients' clinical characteristics, including age, histological grade, pathologic type, lymph node metastasis, and FIGO stage (2018) and compared them by chi-square test. All patients were followed for 5.5 to 6.8 years. Kaplan-Meier method and log-rank test were used to compare the differences in the overall survival (OS) and progression-free survival (PFS) among the different groups. RESULTS: Overexpression of UBQLN4 was observed in 70.9% (83/117) of all cervical cancer tissues and in 15.6% (5/32) of the paired parauterine tissues. The expression of UBQLN4 was associated with lymph node metastasis, poor differentiation, and advanced stage, but the difference was not significant. Kaplan-Meier and log-rank test results suggested the high expression of UBQLN4 was associated with short OS and PFS. Regardless of UBQLN4 expression, the patient age and FIGO stage were also associated with disease prognosis. The statistically significant variables obtained from univariate the Kaplan-Meier analysis were subjected to Cox multivariate survival regression analysis, which showed that, in addition to the FIGO stage and age, UBQLN4 was also an independent prognostic marker for OS and PFS (P = 0.011 and P = 0.024, respectively). CONCLUSION: The overexpression of UBQLN4 was associated with poor prognosis in cervical cancer. Our study proposed a novel prognostic factor and improved the existing understanding of the pathogenesis of cervical cancer.

LncRNA TCF7 Promotes Epithelial Ovarian Cancer Viability, Mobility and Stemness via Regulating ITGB8.

This study aimed to investigate the carcinogenic role of long non-coding RNA T-cell factor 7 (lnc-TCF7) in epithelial ovarian cancer (EOC). Lnc-TCF7 overexpression and shRNA plasmids were transfected into SKOV3 and OVCAR3 cells, followed by measurement of cell proliferation, migration, invasion, apoptosis, stemness, and mRNA profile (via microarray). Besides, lnc-TCF7 expression was measured in tumor and adjacent tissues from 76 EOC patients. Lnc-TCF7 was upregulated in EOC cell lines; its overexpression increased cell proliferation, migration, invasion, but decreased apoptosis and promoted CD44, CD133 expressions, CD44+CD133+ cell proportion, spheres formation efficiency and drug resistance to cisplatin in SKOV3 and OVCAR3 cells. Besides, lnc-TCF7 ShRNA exhibited opposite effects comparing with its overexpression. Microarray analysis revealed 267 mRNAs were modulated by lnc-TCF7 dysregulation, among which ITGB8 was the most dysregulated one, which was validated by subsequent western blot and RT-qPCR. Furthermore, ITGB8 overexpression not only induced proliferation, migration, invasion and stemness, but also attenuated the effect of lnc-TCF7 ShRNA on these functions in SKOV3 and OVCAR3 cells. In addition, lnc-TCF7 was upregulated in tumor tissues and correlated with higher pathological grade, tumor size, International Federation of Gynecology and Obstetrics (FIGO) stage and worse overall survival in EOC patients. Conclusively, lnc-TCF7 regulates multiple oncogenic pathways, promotes proliferation, migration, invasion, stemness via upregulating ITGB8. It also correlates with advanced tumor features and poor prognosis in EOC, implying its potential as a target for EOC treatment.

Circ_0007841 accelerates ovarian cancer development through facilitating MEX3C expression by restraining miR-151-3p activity.

The critical importance of circular RNAs (circRNAs) in human cancers, including ovarian cancer, has been discovered in the recent years. However, the roles of circ_0007841 in ovarian cancer remain unknown. In the current study, it was found that circ_0007841 expression was upregulated in ovarian cancer tissues and cell lines. Upregulation of circ_0007841 in patients with ovarian cancer predicts poor prognosis. Loss-of-function experiments discovered that circ_0007841 knockdown suppressed the proliferation, migration and invasion of ovarian cancer cells in vitro and in vivo. In terms of mechanism, circ_0007841 worked as a competing endogenous RNA (ceRNA) for miR-151-3p to facilitate MEX3C expression. Restoration of MEX3C level recovered the proliferation, migration and invasion of ovarian cancer cells. In conclusion, this study demonstrated that circ_0007841/miR-151-3p/MEX3C axis exerted important oncogenic functions in ovarian cancer.

Model predictive control of azeotropic dividing wall distillation column for separating furfural-water mixture.

Dividing wall distillation columns (DWDCs) are effective technologies for distillation process intensifications. Azeotropic DWDCs (ADWDCs) are effective process intensification technologies to further intensify distillation process through combination of azeotropic distillation (AD) with DWDC. Investigations on the controllability and operation ability of ADWDC are mainly employing the traditional proportional-integral (PI) control schemes. Because of the inherent complicated configuration of ADWDC, the PI control leads to relatively poor dynamic performances. So as to enhance the dynamic performances, composition control scheme employing the advanced model predictive control (MPC) for an ADWDC separating furfural and water is studied in this paper. Although there are several studies employing MPC for DWDC, few investigation has been done on using MPC for ADWDC which is more interactive than DWDC. The dynamic results obtained in this paper using MPC are compared with the corresponding PI control scheme. Although the steady-state deviations and numbers of oscillations are similar employing PI control and MPC, the settling time and maximum deviations are smaller using MPC. MPC can considerably suppress the maximum deviation in face of +20% feed flow rate disturbance from -1.449% to -0.013%, and the corresponding settling time is reduced from 4.28 h to 2.20 h. These prove that MPC is more suitable than PI control for ADWDC. This paper provides new effective control scheme for the complex and highly interactive ADWDC, and verifies that MPC is a promising method for ADWDC to provide better dynamic performances with reduced maximum deviations and shortened settling time.

NR2F2-AS1 accelerates cell proliferation through regulating miR-4429/MBD1 axis in cervical cancer.

Cervical cancer is one of the most frequent malignant tumors in female. Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play a key role in the development of multiple cancers. Although some studies have confirmed that lncRNA NR2F2 antisense RNA 1 (NR2F2-AS1) is a pro-cancer gene in many cancers, the molecular mechanism of NR2F2-AS1 in cervical cancer has not been completely elucidated. In the present study, our results revealed that NR2F2-AS1 expression was up-regulated in cervical cancer tissues and cells, notably in patients with advanced cervical cancer. NR2F2-AS1 accelerated progression of cervical cancer by facilitating cell proliferation, migration, invasion, and EMT process, but inhibiting cell apoptosis. Moreover, NR2F2-AS1 acted as a molecular sponge of miR-4429 and methyl-CpG-binding domain protein 1 (MBD1) was a downstream target of miR-4429 in cervical cancer. Furthermore, there was a negative correlation between miR-4429 expression and NR2F2-AS1 or MBD1 expression in tumor tissues. Rescue experiments confirmed that MBD1 overexpression partly rescued NR2F2-AS1 knockdown-mediated inhibition of progression in cervical cancer. To sum up, these results suggested the potential mechanism of NR2F2-AS1 in cervical cancer and revealed that NR2F2-AS1 exerted its carcinogenic effect via regulating miR-4429/MBD1 axis, indicating a promising insight into the therapeutic target of cervical cancer.

Long non-coding RNA RP11-552M11.4 promotes cells proliferation, migration and invasion by targeting BRCA2 in ovarian cancer.

The present study aimed to investigate the effect of long non-coding RNA (lncRNA) RP11-552M11.4 on cell proliferation, apoptosis, migration and invasion as well as its targeting genes in epithelial ovarian cancer (EOC) cells. LncRNA RP11-552M11.4 expression was detected in 67 tumor tissues and paired adjacent tissues obtained from EOC patients. lncRNA RP11-552M11.4 mimic/inhibitor plasmids were transferred into ovarian cancer cells (SKOV3, A-2780) and normal ovarian epithelial cells (IOSE80 cells). In addition, rescue experiment was carried out by transferring BRCA2 inhibitor&lncRNA RP11-552M11.4 inhibitor plasmids into SKOV3 and A-2780 cells. qPCR, western blot, CKK-8, Annexin V/propidium iodide (AV/PI), wound-healing and Matrigel invasion assays were carried out to detect RNA expression, protein expression, cell proliferation, apoptosis, migration, and invasion, respectively. LncRNA RP11-552M11.4 expression was elevated in tumor tissues compared with paired adjacent tissues and correlated with higher pathological grade, International Federation of Gynecology and Obstetrics stage and worse overall survival in EOC patients. LncRNA RP11-552M11.4 promoted SKOV3 cell proliferation, migration and invasion whereas it inhibited apoptosis. Rescue experiment and luciferase reporter assay showed that lncRNA RP11-552M11.4 regulated SKOV3 cells functions through binding BRCA2. Further experiments in A-2780 cells also validated that lncRNA RP11-552M11.4 induced A-2780 cell proliferation while repressing apoptosis by targeting BRCA2. In addition, upregulation of lncRNA RP11-552M11.4 increased IOSE80 cell proliferation, migration and invasion while decreasing apoptosis. In conclusion, lncRNA RP11-552M11.4 correlates with worse prognosis, and promotes cell proliferation, migration, invasion, and inhibits cell apoptosis by down-regulating BRCA2 in EOC.

Overexpression of MMSET in endometrial cancer: a clinicopathologic study.

BACKGROUND AND OBJECTIVES: Endometrial cancer is a common gynecologic malignancy. It has been reported that overexpression of multiple myeloma SET (MMSET) promoted cellular adhesion, clonogenic growth, and tumorigenicity in other carcinomas. Therefore, the authors expected to investigate whether MMSET overexpression is an independent prognostic marker in endometrial cancer. METHODS: Immunohistochemistry was performed to examine the expression of MMSET in 161 endometrial cancer specimens and 62 normal endometrium specimens. The correlation of MMSET expression with clinicopathological parameters was assessed using χ(2) analysis. Patients' survival was analyzed using the Kaplan-Meier and log-rank tests. Cox regression was used for the multivariate analysis of prognostic factors. RESULTS: MMSET immunoreactivity was overexpressed in endometrial cancer compared with normal endometrium (P < 0.001). Moreover, MMSET expression was correlated with FIGO stage, histological grade, depth of myometrial invasion, lymph node metastasis, and vascular/lymphatic invasion. Furthermore, Patients with positive MMSET expression had significantly poorer overall survival and disease-free survival compared with patients with negative expression of MMSET (both P < 0.001, log-rank test). Multivariate Cox regression analysis revealed that positive MMSET expression was an independent prognostic factor for both OS and DFS of patients with endometrial cancer (P = 0.008 and P = 0.048, respectively). CONCLUSIONS: Overexpression of MMSET may contribute to the progression of endometrial cancer and also may serve as a new biomarker to predict the prognosis of endometrial cancer.

Overexpression of the HIF hydroxylase PHD3 is a favorable prognosticator for gastric cancer.

Hypoxia-induced factors (HIFs) play a central role in the adaptive mechanisms of cancer cells to survive under conditions of hypoxia. HIFs are regulated by prolyl hydroxylases (PHDs) among which PHD3 is implicated as a tumor suppressor. We aimed to correlate PHD3 expression with clinicopathologic parameters and to evaluate its prognostic significance in gastric cancer. The 101 tissue samples were collected from 83 resected stages I­IV gastric cancer patients, which were grouped as non-cancerous mucosa (n=18) and primary carcinoma (n=83). PHD3 expression was evaluated by immunohistochemistry. We adopted Pearson chi-square test, univariate analysis, multivariate analysis and Kaplan­Meier method. The positive frequency of PHD3 in cancer cells was 42.2%, whereas non-cancerous mucosa had no detectable PHD3. The expression of PHD3 increased significantly from non-cancerous mucosa to cancer. A significant difference was observed between PHD3 expression and tumor differentiation (P=0.007). The overexpression of PHD3 was associated with well differentiation. In univariate analyses, American Joint Committee on Cancer (AJCC) stage (P<0.0001), pT classification (P<0.0001), pN classification (P<0.0001), differentiation (P=0.0121), peritoneal metastasis (P=0.0006) and gross features (P=0.0104) were significantly associated with survival except PHD3 (P=0.2228) (Table 3). In multivariate analysis, AJCC stage was prognostically independent [hazard ratio (HR), 3.078; 95% confidence interval (CI), 2.228­4.252; P<0.0001]. Overexpression of PHD3 is a favorable prognosticator for gastric cancer. AJCC stage is an independent prognostic factor of gastric cancer.

The relevance and role of vascular endothelial growth factor C, matrix metalloproteinase-2 and E-cadherin in epithelial ovarian cancer.

We investigated the correlation of vascular endothelial growth factor C, matrix metalloproteinase-2, E-cadherin to explore mechanisms of vascular endothelial growth factor C in the metastasis of ovarian cancer and the relationship of prognosis. We applied immunohistochemistry to investigate the expression of vascular endothelial growth factor C, matrix metalloproteinase-2 and E-cadherin in ovarian tissues of 227 patients. We adopted Pearson chi-square test, Spearman correlation coefficient, univariate analysis, multivariate analysis, and Kaplan-Meier method. The positive rate of vascular endothelial growth factor C, matrix metalloproteinase-2 and E-cadherin in ovarian cancer was higher than that in borderline and benign tumor (P < 0.01). Vascular endothelial growth factor C was positively correlated with matrix metalloproteinase-2 (r = 0.665, P < 0.01) while negatively with E-cadherin(r = -0.185, P < 0.05). Univariate analysis showed clinical stage, pathologic grade, lymphatic metastasis, residual disease, chemotherapy, ascites, vascular endothelial growth factor C, and matrix metalloproteinase-2-influenced survival time (P < 0.05). In Cox multivariate analysis, all the aforementioned factors were found to be independent prognostic factors except pathologic grade. Vascular endothelial growth factor C was a new target to assess the prognosis of ovarian cancer. The expression of vascular endothelial growth factor C in ovarian cancer was related to matrix metalloproteinase-2 and E-cadherin.