Exosomal circ_0048856 derived from non-small cell lung cancer contributes to aggressive cancer progression through downregulation of miR-1287-5p.

AIM: Present study was aimed to explore the diagnostic value and mechanism of exosome derived circular RNA (circ)_0048856 in non-small cell lung cancer (NSCLC) development. METHODS: Exosomes protein markers, CD63 and CD9, were examined by Western blot. Real time quantitative reverse transcriptase - polymerase chain reaction (qRT-PCR) was used to detect the relative expression of circ_0048856 and miR-1287-5p. Proliferation of NSCLC cell was detected by MTT assay. Transwell assay was utilized to evaluated the migration and invasion of NSCLC cells. Apoptosis rate was examined by Flow cytometry. Double luciferase report assay was used to assess the targeting association between circ_0048856 and miR-1287-5p. Diagnostic value of circ_0048856 for NSCLC was estimated by receiver operating characteristic (ROC) curve. Animal models were constructed to explore the function of exosomal circ_0048856 in NSCLC. RESULTS: Diameter of exosomes in NSCLC serum was ranged between 75 and 150 nm. Exosomes circ_0048856 was enhanced in NSCLC serum and cell lines (P < 0.001). Exosome derived circ_0048856 had high diagnostic value for NSCLC. Area under the curve (AUC) was 0.943 (95%CI=0.904-0.982, P < 0.001). at the optimal cutoff value of 1.800, the sensitivity was 0.880, and specificity was 0.800. Exosome circ_0048856 facilitated proliferation, migration and invasion, inhibited apoptosis of NSCLC cells. MiR-1287-5p could be effaced by circ_0048856. MiR-1287-5p reversed the biological behavior changes of NSCLC cells which induced by circ_0048856. In vivo, exosomal circ_0048856 could significantly promote tumor growth (P < 0.001). CONCLUSION: Exosomes derived circ_0048856 was elevated in NSCLC serum and cell lines. Exosome circ_0048856 promoted the NSCLC development by targeting miR-1287-5p. Exosome circ_0048856 had high diagnostic value for NSCLC.

MicroRNA-124 suppresses the invasion and proliferation of breast cancer cells by targeting TFAP4.

MicroRNA (miRNA/miR)-124 is widely accepted as the suppressor of different tumors. The present study aimed to improve understanding of the potential role of miR-124 in breast cancer. The gene expression profile change derived from the overexpression of miR-124 was investigated using RNA sequencing and bioinformatics analysis of the breast cancer cell line SKBR3. The results demonstrated that the gene expression profile of SKBR3 cells significantly changed. In addition, the transcription factor activating enhancer-binding protein 4 (TFAP4) gene was identified among the top 10 differentially expressed genes, and was identified as a novel target gene of miR-124 using a dual-luciferase reporter assay. TFAP4 knockdown in notably impaired SKBR3 cell migration and proliferation, which was consistent with decreasing migration and proliferation ability following overexpression of miR-124. Taken together, these results suggest that overexpression of miR-124 can suppress the migration and proliferation of SKBR3 cells by tarsgeting TFAP4. Thus, TFAP4 may act as a novel therapeutic target of breast cancer.

Long non-coding RNA PRNCR1 modulates non-small cell lung cancer cell proliferation, apoptosis, migration, invasion, and EMT through PRNCR1/miR-126-5p/MTDH axis.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly malignant tumor. Accumulating evidence suggested that prostate cancer non-coding RNA 1 (PRNCR1) participated in the pathogenesis of NSCLC, whereas the elaborate mechanism remains unclear. Hence, the role of PRNCR1 in the progression of NSCLC was investigated. METHODS: Levels of PRNCR1, microRNA-126-5p (miR-126-5p), and metadherin (MTDH) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured using Cell Counting Kit-8 (CCK-8). Flow cytometry was conducted to determine cell apoptosis. Besides, transwell assay was performed to detect cell migration and invasion in NSCLC cells. The expression levels of E-cadherin, N-cadherin, Vimentin, and MTDH were detected via Western blot. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull down assays were employed to verify the relationship between miR-126-5p and PRNCR1 or MTDH. RESULTS: PRNCR1 and MTDH levels were highly expressed, while miR-126-5p expression was lowly expressed in NSCLC tissues and cell lines. Knockdown of PRNCR1 promoted cell apoptosis, impeded proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in NSCLC cells, and these effects were abrogated by its target gene of miR-126-5p inhibitor. Moreover, MTDH as the target of PRNCR1, its overexpression reversed the impacts of miR-126-5p mimic on cell behaviors and EMT in vitro. Finally, PRNCR1 and miR-126-5p regulated MTDH expression. CONCLUSION: PRNCR1 modified cell behaviors and EMT via miR-126-5p/MTDH axis in NSCLC cells, providing a novel thinking for clinical treatment of NSCLC.