Long non-coding RNA NRSN2-AS1 promotes ovarian cancer progression through targeting PTK2/ß-catenin pathway.

As a common malignant tumor among women, ovarian cancer poses a serious threat to their health. This study demonstrates that long non-coding RNA NRSN2-AS1 is over-expressed in ovarian cancer tissues using patient sample and tissue microarrays. In addition, NRSN2-AS1 is shown to promote ovarian cancer cell proliferation and metastasis both in vitro and in vivo. Mechanistically, NRSN2-AS1 stabilizes protein tyrosine kinase 2 (PTK2) to activate the ß-catenin pathway via repressing MG-53-mediated ubiquitinated degradation of PTK2, thereby facilitating ovarian cancer progression. Rescue experiments verify the function of the NRSN2-AS1/PTK2/ß-catenin axis and the effects of MG53 on this axis in ovarian cancer cells. In conclusion, this study demonstrates the key role of the NRSN2-AS1/PTK2/ß-catenin axis for the first time and explores its potential clinical applications in ovarian cancer.

Construction of a prognostic model for triple-negative breast cancer based on immune-related genes, and associations between the tumor immune microenvironment and immunological therapy.

BACKGROUND: Triple-negative breast cancer (TNBC) is the subtype of breast cancer with the worst prognosis, and it is highly heterogeneous. There is growing evidence that the tumor immune microenvironment (TIME) plays a crucial role in tumor development, maintenance, and treatment responses. Notably however, the full effects of the TIME on prognosis, TIME characteristics, and immunotherapy responses in TNBC patients have not been fully elucidated. METHODS: Gene Expression Omnibus and The Cancer Genome Atlas data were used to data analysis. Single-cell sequencing and tissue microarray analysis were used to investigate gene expression. The concentrations and distributions of immune cell types were determined and analyzed using the CIBERSORT strategy. Tumor immune dysfunction and exclusion score and the IMvigor210 cohort were used to estimate the sensitivity of TNBC patients with different prognostic statuses to immune checkpoint treatment. RESULTS: Five immune-related genes associated with TNBC prognosis (IL6ST, NR2F1, CKLF, TCF7L2, and HSPA2) was identified and a prognostic evaluation model was constructed based on those genes. The respective areas under the curve of the prognostic nomogram model at 3 and 5 years were 0.791 and 0.859. The group with a lower nomogram score, with a better prognosis survival status and clinical treatment benefit rate. CONCLUSION: A prognostic model for TNBC that was closely related to the immune landscape and therapeutic responses was constructed. This model may help clinicians to make more precise and personalized treatment decisions pertaining to TNBC patients.

BMI-1 promotes breast cancer proliferation and metastasis through different mechanisms in different subtypes.

Breast cancer is among the most common malignant cancers in women. B-cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) is a transcriptional repressor that has been shown to be involved in tumorigenesis, the cell cycle, and stem cell maintenance. In our study, increased expression of BMI-1 was found in both human triple negative breast cancer and luminal A-type breast cancer tissues compared with adjacent tissues. We also found that knockdown of BMI-1 significantly suppressed cell proliferation and migration in vitro and in vivo. Further mechanistic research demonstrated that BMI-1 directly bound to the promoter region of CDKN2D/BRCA1 and inhibited its transcription in MCF-7/MDA-MB-231. More importantly, we discovered that knockdown of CDKN2D/BRCA1 could promote cell proliferation and migration after repression by PTC-209. Our results reveal that BMI-1 transcriptionally suppressed BRCA1 in TNBC cell lines whereas, in luminal A cell lines, CDKN2D was the target gene. This provides a reference for the precise treatment of different types of breast cancer in clinical practice.

Long Non-coding RNA RP11-395G23.3 Acts as a Competing Endogenous RNA of miR-124-3p to Regulate ROR1 in Anaplastic Thyroid Carcinoma.

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies with poor prognosis. However, the underlying mechanisms of ATC remain to be elucidated. Recently, increasing studies have focused on competitive endogenous RNA (ceRNA) to discover valuable biomarkers for the diagnosis of ATC. The present study identified 705 differentially expressed mRNAs and 47 differentially expressed lncRNAs. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. Additionally, an lncRNA/miRNA/mRNA network was constructed which included 1103 regulatory relations. The upregulation of RP11-395G23.3 in ATC cells was confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). In the loss of function assays, results suggested silencing of RP11-395G23.3 inhibited cell proliferation and induced cell apoptosis. Mechanically, RP11-395G23.3 could increase ROR1 via sponging miR-124-3p as a ceRNA. Moreover, ROR1 expression was decreased with the downregulation of RP11-395G23.3, but was rescued by the co-transfection of the miR-124-3p inhibitor in ATC cells. Our research suggested that the RP11-395G23.3/miR-124-3p/ROR1 axis potentially acted as a potential target for the diagnosis of ATC.