LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer.

Long noncoding RNAs (lncRNAs) are critically involved in the occurrence and development of breast cancer (BC). In this study, we performed RNA sequencing, and the results revealed an increase in the expression level of novel lncRNA ENST00000370438 in tissues of patients with BC. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) results showed an increase in lncRNA ENST00000370438 expression level in 23 pairs of BC tissues. Next, we determined the effect of ENST00000370438 on BC cell proliferation, and the results showed that ENST00000370438 promotes cell proliferation in BC. The proteomic analysis showed a decrease in DHCR24 expression level in BC cells transfected with ENST00000370438 small interfering RNA. Western blot and qRT-PCR assay results showed that ENST00000370438 regulated DHCR24 expression. Furthermore, the rescue experiment showed that the interference with ENST00000370438 expression could restore the effect of DHCR24 overexpression on BC cell proliferation, demonstrating that ENST00000370438 could promote cell proliferation by upregulating DHCR24. Finally, we showed that lncRNA ENST000000370438 could promote tumor growth by overexpressing DHCR24 in nude mice. Our results demonstrated that lncRNA ENST00000370438 promotes BC cell proliferation by upregulating DHCR24 expression.

Tumor-derived exosomal linc00881 induces lung fibroblast activation and promotes osteosarcoma lung migration.

Osteosarcoma (OS) commonly metastasizes to the lung, yet the underlying molecular mechanisms remain poorly understood. Exosomes play a crucial role in tumor migration, including OS lung migration. However, the underlying mechanism by which exosome-derived long non-coding RNAs (lncRNAs) contribute to lung migration in osteosarcoma (OS) remains unclear. This study presents a newly discovered lncRNA, linc00881, derived from OS exosomes. Our study shows that linc00881 promotes the migration of OS cells to the lung and induces the conversion of normal lung fibroblasts into cancer-associated fibroblasts (CAFs). Subsequently, we found that exosomal linc00881 secreted by OS cells can regulate the expression of matrix metalloproteinase 2 (MMP2) in HFL-1 cells by sponging miR-29c-3p, thereby activating the NF-κB signaling in lung fibroblasts. Finally, we discovered that pro-inflammatory cytokines, namely IL-1ß, IL-6, and IL-8, were secreted through the linc00881/miR-29c-3p/MMP2 axis. These results suggest that OS-derived exosomes can mediate the intercellular crosstalk between OS cells and lung fibroblasts, ultimately impacting OS lung migration. Our study provides a potential target for the treatment of OS lung migration.

lncRNA ENST00000422059 promotes cell proliferation and inhibits cell apoptosis in breast cancer by regulating the miR-145-5p/KLF5 axis.

Krüppel-like zinc-finger transcription factor 5 (KLF5) is a vital regulator of breast cancer (BC) onset and progression. The mechanism by which KLF5 regulates BC is still not clearly known. In this study, bioinformatics analysis shows that BC-affected individuals with elevated KLF5 expression levels have poor clinical outcomes. We further verify that miR-145-5p regulated KLF5 expression to promote cell apoptosis and inhibit cell proliferation in BC via dual-luciferase reporter assay, western blot analysis, qRT-PCR, CCK-8 assay and cell apoptosis assay. In addition, based on bioinformatics analysis, the binding of ENST00000422059 with miR-145-5p is confirmed by dual-luciferase reporter assay. Subsequently, FISH, western blot analysis, qRT-PCR, CCK-8 and cell apoptosis assays verified that ENST00000422059 increases KLF5 protein expression by sponging miRNA to promote cell proliferation and inhibit cell apoptosis. Finally, ENST00000422059 is found to accelerate tumor progression by regulating the miR-145-5p/KLF5 axis in vivo. In conclusion, this study suggests that ENST00000422059 upregulates KLF5 by sponging miR-145-5p to promote BC progression.

miR-200a-3p promoted cell proliferation and metastasis by downregulating SOX17 in non-small cell lung cancer cells.

Lung cancer has high mortality and incidence rates in which non-small cell lung cancer (NSCLC) is the primary type of lung cancer that accounts for about 80%-85% of total patients. It has been demonstrated that microRNAs (miRNAs) are critical in the incidence and progression of tumors, while the role and inner mechanism of miR-200a-3p, one type of essential miRNAs, in NSCLC have yet to be revealed. Herein, we investigated the in vitro and vivo pro-/antiproliferative influence of miR-200a-3p on NSCLC cells and utilized bioinformatic programs to further predict the SOX17 gene as miR-200a-3p's potential target. A double luciferase reporter gene experiment was performed to confirm that miR-200a-3p interacts with the SOX17 3'-UTR region specifically. On the basis of the results of Western blot and quantitative reverse-transcription polymerase chain reaction (qRT-PCR), miR-200a-3p impacted the posttranscriptional levels of SOX17 rather than influencing its mRNA expression. In the end, we found that overexpressed SOX17 can reverse miR-200a-3p's impact on NSCLC cell proliferation and metastasis. Therefore, this study demonstrated that miR-200a-3p influences NSCLC cell proliferation and metastasis by modulating the levels of SOX17.

miR-125b-5p upregulation by TRIM28 induces cisplatin resistance in non-small cell lung cancer through CREB1 inhibition.

OBJECTIVE: miR-125b-5p plays an important role in the development of cancer and drug resistance. However, in cisplatin resistance of non-small cell lung cancer (NSCLC), the function and potential mechanism of miR-125b-5p is still unclear. The aim of this study was to investigate the role and molecular mechanism of miR-125b-5p in cisplatin resistance of NSCLC. METHODS: A GEO dataset (GSE168707) was analyzed to find high miR-125b-5p levels were associated with DDP resistance. miR-125b-5p expression levels were detected in A549 and A549/DDP cells via real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays, western blots and mouse model xenografted were performed to identify CREB1 as a direct target gene of miR-125b-5p. Cell proliferation and apoptosis were also performed to identify whether miR-125b-5p upregulation by TRIM28 induces DDP resistance in NSCLC through CREB1 inhibition. RESULTS: In A549/DDP cells, miR-125b-5p expression was upregulated compared to A549 cells. Then miR-125b-5p was found to increase DDP resistance in NSCLC in vivo and in vitro by increasing cell proliferation and suppressing cell apoptosis. Bioinformatic analyses were used to search for gene which miR-125b-5p can target. We identified miR-125b-5p can regulate CREB1 via luciferase reporter assays, qRT-PCR and western blots. Cell proliferation and apoptosis were also performed to confirm miR-125b-5p could impact on CREB1 and induce the DDP resistance in NSCLC. Additionally, we used bioinformatic analyses to find tripartite motif-containing 28 (TRIM28) as a transcriptional enhance factor of miR-125b-5p. The expression of TRIM28 was upregulated in A549/DDP cells compared with that in A549 cells by qRT-PCR. Finally, we found TRIM28 could mediate DDP resistance through miR-125b-5p/CREB1 axis via cell proliferation, western blot and apoptosis assay. CONCLUSIONS: Overall, our findings demonstrated novel functions and mechanisms underlying DDP resistance in NSCLC through the TRIM28/miR-125b-5p/CREB1 axis. These may serve as novel therapeutic targets to improve the treatment efficacy using DDP for NSCLC in the future.