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Long non-coding RNAs (lncRNAs) have been identified as critical players in tumorigenesis. Previous studies revealed that lncRNA SBF2-AS1 was involved in tumor progression. However, the role and underlying mechanism of SBF2-AS1 in cervical cancer (CC) remain unknown. In the present study, our data showed that SBF2-AS1 expression was significantly increased in CC. High SBF2-AS1 expression was associated with advanced FIGO stage and lymph node metastasis of CC patients. Function assays showed that SBF2-AS1 inhibition significantly reduced CC cells proliferation both in vitro and in vivo. Mechanistically, we showed that SBF2-AS1 upregulation restrained the activity of miR-361-5p and led to overexpression of FOXM1 in CC cells. Furthermore, we found that miR-361-5p inhibitors could rescue the effects of SBF2-AS1 inhibition on CC cells proliferation. Taken together, we demonstrated that the SBF2-AS1/miR-361-5p/FOXM1 axis might play an important role in CC progression. SBF2-AS1 might serve as a potential therapeutic target for CC treatment.

Long noncoding RNA lung cancer associated transcript 1 (LUCAT1) has been shown to be a lncRNA that facilitates the development and progression of several tumours. However, the evidence of LUCAT1 modulating the growth and metastasis of cervical cancer (CC) were still lacking. The present study aimed to explore the expression pattern, biological function and potential mechanism of LUCAT1 in CC. In this study, we, first, confirmed that LUCAT1 acted as an up-regulated lncRNA by analyzing the data from GCTA dataset and RT-PCR in both CC tissues and cell lines. We also showed that TINCR overexpression is induced by nuclear transcription factor SP1. Then, clinical assays showed that LUCAT1 was associated with advanced clinical progression and poor prognosis of CC patients. Importantly, multivariate Cox model confirmed that LUCAT1 expression was an independent prognostic factor for both 5-year overall survival in CC. Then, lost-function assays revealed that knockdown of LUCAT1 significantly suppressed CC cells proliferation, colony formation, migration, invasion and EMT by a series of cells experiments. Mechanistically, Bioinformatic tools predicted that miR-181a may target LUCAT1, which was confirmed using luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Overall, our findings showed that SP1-activated LUCAT1 exerts an oncogenic function in CC by binding to miR-181a, suggesting that miR-181a may be a ponderable and promising therapeutic target for CC.

BACKGROUND Ovarian cancer is one of the most common gynecological malignancies and mortality ranks the highest in cancer-associated death in females' worldwide. Here, we attempted to evaluate the effect of DANCR on the biological behavior of transforming growth factor-s (TGF-s) stimulated ovarian cancer cells. MATERIAL AND METHODS The expression of DANCR in ovarian cancer cells (A2780 and SKOV3) treated with TGF-s were detected by quantitative real-time polymerase chain reaction (qRT-PCR). DANCR silencing was constructed using lentiviral transfection in ovarian cancer cells. The Cell Counting Kit-8 (CCK-8), flow cytometry and Transwell assays were performed to measure some cytology index. Western blot was utilized to explore the effect of DANCR on Kruppel-like factor 5 (KLF5) expression. RESULTS The expression of DANCR in cancer cells (A2780 and SKOV3) treated with TGF-s was significantly higher. DANCR silencing suppressed cell viability, migration and invasion, and induced cell apoptosis of TGF-s treated ovarian cancer cells. Bioinformatics analysis showed that DANCR served as a sponge for miR-214, and also showed that KLF5 was targeted by miR-214. In addition, DANCR could inhibit the expression of KLF5. CONCLUSIONS We are the first to report that knockdown of DANCR could affect the biological process of ovarian cancer cells treated with TGF-s by sponging miR-214, which may provide new therapeutic ideas of ovarian cancer.

In this study, we aimed to assess the independent prognostic value of miR-361-3p in terms of overall survival (OS) and recurrence-free survival (RFS) in cervical cancer, as well as its possible regulative network. A retrospective analysis was performed by using data from the Cancer Genome Atlas-Cervical Cancer (TCGA-CESC). Results showed that decreased miR-361-3p expression was associated with lymphovascular invasion and poor responses to primary therapy. The patients with recurrence and the deceased cases had substantially lower miR-361-3p expression compared to their respective controls. By generating Kaplan-Meier curves of OS and RFS, we found that high miR-361-3p expression was associated with better survival outcome. More importantly, univariate and multivariate analysis confirmed that high miR-361-3p expression was an independent indicator of favorable OS (HR: 0.377, 95% CI: 0.233–0.608, p<0.001) and RFS (HR: 0.398, 95% CI: 0.192–0.825, p=0.013). By performing bioinformatic analysis, we identified 24 genes that were negatively correlated with miR-361-3p expression. Among the potential targeting genes, SOST, MTA1, TFRC, and YAP1 are involved in some important signaling pathways modulating cervical cancer cell invasion, migration, and drug sensitivity. Therefore, it is meaningful to verify the potential regulative effect of miR-361-3p on the expression of these genes in the future.

Circular RNAs (circRNAs) have been shown to be involved in the development of cancer. The aim of the present study was to investigate the role of circRNA SMARCA5 (cSMARCA5) in human cervical cancer. In the present study, cSMARCA5 expression was upregulated in cervical cancer tissues and cell lines. Furthermore, the proliferation rate of cells transduced with viral plasmids expressing small interfering RNA targeting cSMARCA5 was downregulated. Bioinformatics analysis predicted that microRNA (miR)‑432 targeted cSMARCA5, and miR‑432 was able to interact with epidermal growth factor receptor (EGFR) by binding to its 3'‑untranslated region. The expression levels of EGFR, ERK1 and ERK2 were increased in cervical cancer tissues. Furthermore, correlation analysis revealed that cSMARCA5 levels were positively correlated with ERK1 and ERK2 levels. In conclusion, the present findings suggested that cSMARCA5 may play an important role in the progression of cervical cancer via the ERK signaling pathway by modulating miR‑432.

In the present study, the function of microRNA (miR)‑195 on abdominal aortic aneurysm (AAA) and its possible mechanism were investigated. Reverse transcription‑quantitative polymerase chain reaction analysis was used to detect the expression of miR‑195 in patients with AAA. The expression levels of miR‑195 in patients with AAA were effectively increased. The present study also used miR‑195 mimics to increase the expression of miR‑195, and ELISA kits and western blot analysis were used to analyze the levels of interleukin (IL)‑1β and IL‑6, and the protein expression levels of matrix metalloproteinase (MMP)‑2, MMP‑9, tumor necrosis factor (TNF)‑α, nuclear factor (NF)‑κB, vascular endothelial growth factor (VEGF), phosphoinositide 3‑kinase (PI3K) and phosphorylated (p‑)Akt. The overexpression of miR‑195 promoted the levels of IL‑1β and IL‑6, induced the protein expression of MMP‑2 and MMP‑9, upregulated the protein expression of TNF‑α and NF‑κB, and suppressed the protein expression levels of VEGF, PI3K and p‑Akt in angiotensin II‑vascular smooth muscle cells. In addition, TNF‑α promoted the pre‑inflammatory effect of miR‑195 on the protein expression levels of TNF‑α and NF‑κB, levels of IL‑1β and IL‑6, and protein expression levels of MMP‑2 and MMP‑9 in the angiotensin II‑vascular smooth muscle cells. Suppression of PI3K promoted the pre‑inflammatory effect of miR‑195 on the protein expression of PI3K, p‑Akt and VEGF, the levels of IL‑1β and IL‑6, and the protein expression of MMP‑2 and MMP‑9 in angiotensin II‑vascular smooth muscle cells. Combined, these results suggested that miR‑195 suppressed AAA inflammation through the TNF‑α/NF‑κB and VEGF/PI3K/Akt pathways.

Epigenetic modulation is an important mechanism of miRNA dysregulation in cervical cancer. In this study, we firstly studied how this mechanism contributes to miR-375 downregulation in cervical cancer cells. Then, we further studied the association between miR-375 and MALAT1 (metastasis associated lung adenocarcinoma transcript 1) in epithelial mesenchymal transition (EMT) of the cancer cells. HPV-16 positive SiHa and CaSki cells were used as in vitro model. Our data showed that HPV-16 E6 positively modulated DNMT1 expression in both SiHa and CaSki cells. Knockdown of DNMT1 partly restored miR-375 levels in the cells. The following methylation-specific PCR (MSP) assay and qRT-PCR analysis showed that methylation was common in the promoter region of miR-375 in both SiHa and CaSki cells and demethylation partly restored miR-375 levels in the cells. Therefore, we infer that miR-375 is downregulated partly due to promoter hypermethylation mediated by DNMT1 in HPV-16 positive cervical cancer cells. Our bioinformatics analysis showed that MALAT1 has three putative binding sites with miR-375 and the following dual luciferase assay confirmed two of them. QRT-PCR analysis showed that miR-375 overexpression significantly reduced MALAT1 expression, while MALAT1 overexpression reversely suppressed miR-375 levels. Therefore, we infer that there is a reciprocal regulation between miR-375 and MALAT1 in the cells. In SiHa cells, miR-375 overexpression or MALAT1 siRNA partly restored E-cadherin expression, significantly reduced N-cadherin and also reduced invasion capacity of SiHa cells. Therefore, these results suggest that miR-375 and MALAT1 form a functional axis modulating EMT in cervical cancer.

MiR-21 is an important microRNA (miRNA) modulating radiosensitivity of cervical cancer cells. However, the underlying mechanism of miR-21 upregulation in radioresistant cervical cancer has not been fully understood. In addition, autophagy may either promote or alleviate radioresistance, depending on the types of cancer and tumor microenvironment. How autophagy affects radiosensitivity in cervical cancer and how miR-21 is involved in this process has not been reported. This study showed that miR-21 upregulation in radioresistant cervical cancer is related to HIF-1α overexpression. MiR-21 overexpression decreases PTEN, increases p-Akt, and subsequently increases HIF-1α expression, while miR-21 inhibition results in increased PTEN, decreased p-Akt, and then decreased HIF-1α. Therefore, we inferred that there is a HIF-1α-miR-21 positive feedback loop through the PTEN/Akt/HIF-1α pathway in cervical cancer cells. In addition, we also demonstrated that miR-21 confers decreased autophagy in cervical cancer cells after IR via the Akt-mTOR signaling pathway. Decreased autophagy is one of the potential mechanisms of increased radioresistance in cervical cancer cells. These findings expand our understanding of radioresistance development in cervical cancer.