MicroRNAs (miRNAs/miRs) are a class of conserved non-coding endogenous small regulatory RNAs that regulate target gene expression by binding to the 3′-untranslated region of target mRNAs in a base-pairing manner, resulting in repression of transcription or degradation of target mRNAs. It has been demonstrated previously that the abnormal expression of miRNAs is involved in the carcinogenesis and progression of cervical cancer. The aim of the present study was to investigate the expression, biological functions and underlying molecular mechanisms of miR-195 in cervical cancer. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of miR-195 in cervical cancer tissues and cell lines. Following transfection, an MTT assay, cell migration and invasion assays, western blot analysis and a dual-luciferase reporter assay were performed in human cervical cancer cells. In the present study, it was identified that miR-195 was downregulated in cervical cancer tissues and cell lines. Additionally, upregulation of miR-195 and knockdown of hepatoma-derived growth factor (HDGF) inhibited proliferation, migration and invasion of cervical cancer cells. Furthermore, a dual-luciferase reporter assay identified that HDGF was a direct target gene of miR-195. RT-qPCR and western blot analysis demonstrated that miR-195 mimic inhibited HDGF expression at the mRNA and protein levels, whereas miR-195 inhibitor enhanced HDGF expression at the mRNA and protein levels. These results indicated that miR-195 targeted HDGF to inhibit the behavior of tumors in cervical cancer. These results also suggested that miR-195 was a potential therapeutic biomarker of cervical cancer.

Background: Increasing evidence has indicated that circular RNAs (circRNAs) play vital roles in modulating tumor progression. However, regulatory roles and underlying mechanisms of circRNA circ_0072995 in epithelial ovarian cancer (EOC) are not well characterized. Results: Circ_0072995 was up regulated in EOC afflicted tissues and cell lines (HO8910 and A2780), and was mainly located in the cytoplasm. The expression of circ_0072995 was associated with the pathological grade of EOC for respective patients. Functional experiments revealed that circ_0072995 promoted EOC cell proliferation, migration, induced apoptosis, as well as enhanced tumorigenesis in vivo. Mechanistic analyses indicated that circ_0072995 may have acted as a sponge of miR-147a such as to relieve repressive effects of miR-147a upon its target CDK6. Conclusions: Our results revealed that circ_0072995 promoted EOC progression through the circ_0072995/miR-147a/CDK6 axis and may represent a strategy for treatment of EOC afflicted patients. Methods: Expression of circ_0072995 was evaluated in 40 EOC tissue samples and cell lines by qRT-PCR. The location of circ_0072995 was determined via nuclear-cytoplasmic fractionation. A series of functional experiments facilitated determinations of effects of circ_0072995 on EOC progression in vitro, and in vivo. Underlying mechanisms and influence of circ_0072995 on EOC were confirmed by bioinformatic analyses, luciferase reporter assays, qRT-PCR, and Western blotting.

N6-methyladenosine (m6A) RNA methylation has been determined to execute crucial functions in tumorigenesis and cancer development. WT1-associated protein (WTAP) has an important “writer” role in m6A modification, and it is also a nuclear protein that colocalizes with splicing factors and plays a critical role in cell function and cancer progression. However, little is known about the role of WTAP in ovarian cancer (OC) and its mechanisms. In this study, we found for the first time that hypoxia-inducible factor (HIF)-1α could positively regulate increased expression of WTAP under hypoxia. And further results revealed that WTAP expression was closely associated with the clinicopathological features of OC, and high expression of WTAP predicted low survival rate in patients with OC. In addition, cell proliferation and invasive capacity were significantly reduced after knockdown of WTAP expression in OC cells. However, cell proliferation and invasive ability were significantly enhanced after overexpression of WTAP. Additionally, we find that WTAP interacts with DGCR8 (a crucial chip protein) to regulate the expression of microRNA-200 (miR-200) in an m6A-dependent way. Further experiments showed that the key glycolysis enzyme HK2 could be positively regulated by miR-200, which significantly affected the intracellular Warburg effect. In conclusion, this is considered uncovered that upregulation of WTAP expression by HIF-1α intercedes with miRNA processing, accelerates the Warburg impact, and advances the event and advancement of tumor, thus giving a novel viewpoint on m6A adjustment in OC movement.

The current standard treatment for ovarian cancer is aggressive surgery followed by platinum-based combination chemotherapy. Recurrence and chemotherapeutic drug resistance are the two main factors that account for the high mortality of most ovarian cancers. Liposomal doxorubicin is primarily used for the treatment of ovarian cancer when the disease has progressed after platinum-based chemotherapy. However, relatively little is known about the genomic changes that contribute to both cisplatin and doxorubicin resistance in high-grade serous ovarian cancer (HGSC) under the selective pressure of chemotherapy. Here, we found that protein tyrosine phosphatase PTPN3 gene expression was substantially increased in both cisplatin and doxorubicin-resistant ovarian cancer cells. Silencing of PTPN3 restored sensitivity to cisplatin and doxorubicin in resistant ovarian cancer cells. Down-regulation of PTPN3 also inhibited cell cycle progression, migration, stemness in vitro and the tumorigenicity of resistant ovarian cancer cells in vivo. Meanwhile, the expression of PTPN3 was found to be regulated by miR-199 in resistant ovarian cancer cells. These findings suggest that PTPN3 promotes tumorigenicity, stemness and drug resistance in ovarian cancer, and thus is a potential therapeutic target for the treatment of ovarian cancer.