Background: miRNA expression acts as a potential biomarker in many diseases including endometrial carcinoma (EC). miR-486-5p dysregulation is observed in several tumor types, but the roles of miR-486-5p in EC are hardly ever studied. Objective: This study aimed to analyze the expression profile of miR-486-5p in tumor tissues and serum samples of patients with EC and explore the target prediction, function analysis and validation in immortal cell lines. Patients and Methods: A total of 42 freshly paired EC tissues, the corresponding adjacent non-neoplastic tissues and serum samples were also collected from patients with EC, and 42 matched normal serum samples were included as control group. The level of miR-486-5p expression was tested by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was determined by colony formation assay and CCK-8 assay. Furthermore, functional evaluation of miR-486-5p on migration was performed by wound-healing assay and invasion was estimated by transwell invasion assay. qRT-PCR, luciferase reporter assay and Western blotting (WB) were performed to verify the targeting of MARK1 by miR-486-5p. Results: miR-486-5p was significantly up-regulated in EC tissues and serum samples, promoting the proliferation, migration and invasive activities of EC cells by targeting MARK1. Conclusion: These data indicated miR-486-5p as a novel molecular biomarker for diagnosing and treating EC, and MARK1 might act as a critical and functional target of miR-486-5p with the implications on cell proliferation, migration and invasiveness of EC tumor cells.

BackgroundThe biological and clinical significance of matrix metalloproteinase-7 (MMP-7) in cervical cancer remains unknown. Here, we investigated the function of MMP-7 in cervical cancer cells and evaluated its clinical significance in both tissues and serum from cervical cancer patients.MethodsFirst, we analyzed the expression of MMP-7 in cervical cancer using Oncomine microarray data and examined its expression in cervical tissues by quantitative real-time polymerase chain reaction and Western blotting. Second, we utilized gene silencing to explore the role of MMP-7 in cells. Finally, we examined the MMP-7 levels in patients with cervical cancer and normal serum by enzyme-linked immunosorbent assay. Moreover, we further investigated the relationship between MMP-7 expression and pathological features.ResultsThe mRNA and protein MMP-7 levels were higher in cervical cancer tissues than in healthy controls. Silencing of MMP-7 significantly decreased cervical cancer cell proliferation, migration, and invasion. The serum MMP-7 levels were significantly higher in cervical cancer patients than in healthy subjects (P<0.01). Further, higher MMP-7 expression was associated with increased lymph metastasis (P=0.021), pathological grade (P=0.039, P=0.047), and clinical stage (P=0.049, P=0.046).ConclusionMMP-7 appears to act as an oncogene in cervical cancer cells and is involved in cell proliferation, migration, and invasion. MMP-7 expression was significantly higher in the tissue and serum of cervical cancer patients compared to healthy individuals and was correlated with increased pathalogical grade, clinical stage, and lymph metastasis. Therefore, our data provide novel evidence that MMP-7 may be a clinically relevant biomarker for cervical cancer.

The present study was designed to evaluate the anticancer effects of withaferin A against the human endometrial cancer via modulation of transforming growth factor-β (TGF-β) signalling. The results of the present study revealed that withaferin A exerts a dose and time-dependent antiproliferative effects against the human KLE endometrial cancer cells with comparatively lower toxicity against the THESCs normal cells. The IC 50 of withaferin A against the KLE endometrial cancer cells was found to 10 μM. The results showed that withaferin A induced apoptosis and G 2 /M cell cycle arrest of the KLE cells which was associated with alteration of the apoptosis and cell cycle related proteins. In addition, the transwell assays showed that the migration and invasion of the KLE cells were inhibited by 53 and 40%, respectively. Finally, the effects of withaferin A were also examined on the TGF-β signalling pathway. The results showed that withaferin A blocked TGF-β-dependent Smad2 phosphorylation and expression of other TGF-β-related proteins in KLE cells. Summing up, the results suggest that withaferin A inhibits the proliferation of the human endometrial carcinoma via TGF-β signalling.

Background: Mounting evidence indicates altered circadian rhythm represents a critical factor affecting carcinogenesis and tumor progression. The circadian gene neuronal PAS domain protein 2 (NPAS2) constitutes a newly discovered prognostic biomarker. NPAS2 dysregulation is found in multiple malignancies, although its functions in uterine corpus endometrial carcinoma (UCEC) remain largely unknown. Objective: To evaluate NPAS2's roles in UCEC and to explore the underlying mechanisms. Methods: NPAS2 transcription levels, patient prognosis, different clinical stages and target microRNAs in UCEC cases were comparatively assessed based on public databases, including UALCAN, GEPIA, TIMER, Kaplan-Meier plotter, starBase database, LinkedOmics and String. Then, qRT-PCR and immunohistochemical analysis were applied to analyze the expression of NPAS2 in UCEC tissue samples. CCK-8, clonogenic assay and flow cytometry were carried out for detecting cell viability, colony formation ability and cell apoptosis, respectively. Results: NPAS2 was upregulated in tissue samples from UCEC cases compared with the corresponding control specimens. NPAS2 overexpression was associated with decreased overall (OS), disease free (DFS) and relapse free (RFS) survival in UCEC. In addition, NPAS2 overexpression was associated with clinical stage, tumor grade, estrogen receptor status, myometrial invasion in UCEC. Furthermore, NPAS2 knockdown or overexpression altered cell proliferation and apoptosis in UCEC. Moreover, NPAS2 showed significant negative correlations with miR-17-5p and miR-93-5p, and positive correlations with miR-106a-5p and miR-381-3p in UCEC. Conclusion: NPAS2 overexpression is associated with poor prognosis and clinicopathological characteristics in UCEC and promotes proliferation and colony formation while inhibiting apoptosis. Finally, NPAS2 is associated with several miRNAs in UCEC.

Ovarian cancer (OVCA) is a common gynecological malignant tumor and the fourth most common female tumor, following breast cancer, cervical cancer and endometrial cancer. Spindle Assembly checkpoint (SAC) can finely control the dynamic balance between kinetosomes and microtubules during mitosis. MAD2L2 is a chromatin binding protein and selective shear body of MAD2, one part of SAC. However, the expression and prognostic values of MAD2L2 in OVCA have not been clarified. GEPIA, UALCAN, cBioPortal, GeneMANIA, DAVID 6.8, Metascape, TIMER, Kaplan-Meier and in vito cell experiments were utilized in this study. MAD2L2 was over expression in OVCA patients and accompanied with poor survival time, especially in grade four patients. MAD2L2’s mRNA alteration way was amplification and ubiquitination was the mainly regulation way. Significant GO term analysis showed that MAD2L2 were located mainly in the organellar ribosome, where they participate primarily in NADH dehydrogenase activity. They also acted as structural constituents in mitochondrial translation elongation. KEGG pathway analysis showed enrichment in the sulfur relay system and ribosome. Four types of immune module were used and the results showed that MAD2L was relate to CD4, CD8, B cell, NK cell and Myeloid dendritic cell. At last, high level of MAD2L2 promoted cell proliferation and migration of OVCA and upregulation of MAD2L2 suppressing ferroptosis process and accompanied by mTOR signaling in OVCA cells. Therefore, suppressing MAD2L2 might be a next choice of treatment of OVCA patients. In addition to the common strategies, like chemotherapy, preventing mTOR signaling might also be a better treatment method in the future.