LncRNA PCAT6 mediates UBFD1 expression via sponging miR-545-3p in breast cancer cells.

Background: LncRNA PCAT6 has been shown to involve in carcinogenesis of different tumors. In this study, we investigated underline mechanism by which PCAT6 promoted breast cancer cell progression. Methods: RIP was used to identify lncRNAs associated with IMP1. Bioinformatics assays were used to predict potential miRNAs that interact with PCAT6 and mRNAs that are targeted by miR-545-3p. RNA-seq and RT-qPCR were used to analyze differential expression of lncRNAs and miRNA-targeted genes. Luciferase reporter and RNA pull-down assays were performed to identify the molecular interactions between PCAT6 and individual miRNAs. The role of PCAT6-mediated cell proliferation and invasion were tested by CCK-8 and transwell assays following loss-of-function and gain-of-function effects. Results: We identified that PCAT6 is one of the lncRNAs that associated with IMP1. PCAT6 not only binds to IMP1, but also acts as a ceRNA to interact with multiple miRNAs, including miR-545-3p. Binding of IMP1 destabilized PCAT6, while competitive interaction with miR-545-3p allowed PCAT6 to positively regulate UBFD1 expression. Silencing UBFD1 mRNA could effectively rescue PCAT6-induced cell proliferation and invasive abilities. Conclusions: Our study provided evidence that PCAT6 activates UBFD1 expression via sponging miR-545-3p to increase carcinogenesis of breast cancer cells. Based on the nature of UBFD1 as a polyubiquitin binding protein, our study suggested that ubiquitin pathway might contribute to breast cancer progression.

LncRNA MACC1-AS1 associates with DDX5 to modulate MACC1 transcription in breast cancer cells.

MACC1 is a master oncogene involved in multiple aspects of cancer metastasis in a broad variety of tumors. However, the molecular mechanism by which MACC1 transcription is regulated remains unclear. Here, we show that in breast cancer cells, lncRNA MACC1-AS1 serves as a cis-factor to up-regulate MACC1 transcription and this regulation increases the cell proliferation potential. Mechanistically, MACC1-AS1 forms a complex with DEAD-Box helicase 5 (DDX5) and simultaneously interacts with the distal region of the MACC1 promoter. The interaction allows its associated DDX5 to spatially contact the MACC1 core promoter and shift from MACC1-AS1 to the core promoter. Moreover, binding of DDX5 to the core promoter results in local recruitment of the transcription factor SP-1, thus enhancing MACC1 transcription. Our findings reveal a molecular mechanism by which MACC1-AS1 cis-regulates MACC1 transcription by interacting with the distal promoter region and delivering DDX5 to the core-promoter of the gene.

Expression of cystatin C in human esophageal cancer.

AIMS AND BACKGROUND: Cystatin C is a member of the cysteine protease inhibitors and its function is to decrease protease activity. A recent study showed that it was aberrantly expressed in many malignant tumors in association with tumor invasion and metastasis. We attempted to detect its expression in esophageal cancer tissues and adjacent reparative normal tissues. METHODS AND DESIGN: Samples of cancers and non-cancerous esophageal tissues were obtained as matched pairs from 30 surgery patients with esophageal cancer and paraffin embedded. The expression of cystatin C in tissues was investigated by immunohistochemistry. Fisher's exact test was used to analyze the relationship between esophageal cancer tissues and adjacent normal tissues. Furthermore, mRNA was extracted, and reverse transcriptase polymerase chain reaction was performed. RESULTS: The intensity of cystatin C immunostaining in tumor tissues was increased compared to that of adjacent normal tissues. mRNA expression of the cystatin C gene was greater in esophageal cancer than in normal tissues (P <0.05). CONCLUSIONS: Our results indicate that cystatin C may play an important role in the pathogenesis and metastasis of esophageal cancer.