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Background: Breast cancer (BC) is a great contributor to cancer-related death. Mounting studies have identified that circular RNAs (circRNAs) play vital roles in cancer cell proliferation, apoptosis and invasion. Here, we explored the effect of circPVT1 on BC development as well as its downstream mechanisms. Methods: qRT-PCR was used to determine the relative expression levels of circPVT1 and miR-29a-3p in BC tissue samples and cell lines. We also analyzed the relevance between pathological indexes and circPVT1 expression level. Human breast cancer cell lines MCF-7 and MDA-MB-231 were taken as cell models. Gain- or loss-of-functional assays of circPVT1 and miR-29a-3p were conducted in BC cell lines to investigate their effects on the cell proliferation, apoptosis, migration and invasion. The protein levels of AGR2, HIF-1α, Bax, Bcl2 and Caspase3 were determined by Western blot. Furthermore, dual-luciferase reporter assay and RNA fluorescence in situ hybridization (FISH) were used to confirm the targeted relationships between circPVT1 and miR-29a-3p, miR-29a-3p and anterior gradient 2 (AGR2). Results: CircPVT1 was highly expressed while miR-29a-3p was lowly expressed in BC tissues and cell lines. Inhibition of circPVT1 or overexpression of miR-29a-3p remarkably suppressed BC cell proliferation, invasion and migration while promoted cell apoptosis. By contrast, circPVT1 upregulation or miR-29a-3p inhibition led to mitigate malignant behaviours of BC cells. Functionally, circPVT1 bound to miR-29a-3p, and AGR2 was a target gene of miR-29a-3p. Overexpressed circPVT1 promoted AGR2 and HIF-1α expression by repressing miR-29a-3p. More importantly, overexpressing AGR2 enhances HIF-1α expression, accompanied with accelerated proliferation, invasion and migration of BC cells. Conclusion: CircPVT1 acts as an oncogene in BC via promoting the growth, invasion, migration and inhibiting apoptosis through miR-29a-3p-mediated AGR2-HIF-1α axis. [ABSTRACT FROM AUTHOR]

Background: Forkhead box protein A1 (FOXA1), acting as a transcriptional activator for liver-specific transcripts, plays a vital part in proliferation, apoptosis and cell cycle. Methods: The mRNA expression of FOXA1 in 90 HCC tissues and matched adjacent non-tumor tissues was determined by qRT-PCR. The downstream and upstream regulators of FOXA1 were identified by bioinformatics analysis and experimental confirmation. Results: We found out that the expression of FOXA1 was obviously higher in hepatocellular carcinoma (HCC) tissues than that in matched non-tumor tissues. Similarly, FOXA1 is also highly expressed in HCC cell lines as compared with normal human hepatic cell line L02. Clinical association analysis indicated that high expression of FOXA1 was prominently correlated with high HBV level, large tumor size, high venous infiltration, high Edmondson–Steiner grading, and advanced tumor-node-metastasis tumor stage. Furthermore, the in vitro tests showed that ectopic expression of FOXA1 promoted HepG2 cell proliferation and suppressed apoptosis. In contrast, the downregulation of FOXA1 inhibited cell proliferation, and induced apoptosis in Hep3B cells. To investigate the functional mechanism of FOXA1, anterior gradient 2 (AGR2), an executor in proliferation and apoptosis, was identified as the direct target gene of FOXA1. Meanwhile, we also found the expression of FOXA1 could be inhibited by miR-212-3p, which working as a tumor suppressor downregulated in HCC. Conclusion: We revealed that FOXA1 exerted its biological function by regulating AGR2 expression, and its ectopic expression may be blamed for low expression of miR-212-3p. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide. LINC00460, a novel long non-coding RNA (lncRNA), was recently confirmed as an oncogene in various cancers. However, the biological function and underlying mechanism of LINC00460 in HCC is largely obscure. Methods: Fifty pairs of tumor tissue and adjacent normal tissues from HCC patients, as well as six HCC cell lines and a normal human hepatic epithelial cell line were subjected to qRT-PCR assay to evaluate the expression levels of LINC00460. CCK-8 assays were used to detect the proliferation of HCC cells. Transwell assay was used to measure the migration and invasion abilities of HCC cells. RNA pull-down and luciferase assays were performed to verify the direct interaction between LINC00460 and miR-342-3p. A xenograft model of HCC was established to validate the in vivo function of LINC00460 in HCC progression. Results: We firstly detected LINC00460 expression was significantly upregulated in both HCC tumor tissues and cell lines. The upregulation of LINC00460 was positively associated with HCC progression. Functionally, LINC00460 facilitated HCC cell proliferation, migration, and invasion capacities, which due to that LINC00460 could physically bind to and repress miR-342-3p to elevate the expression of AGR2. Conclusion: Our data firstly reveal the clinical relevance, biological function, and regulatory mechanism of LINC00460 in HCC development. LINC00460 promotes HCC progression by elevating AGR2 expression via sponging miR-342-3p, providing a promising therapeutic target for HCC treatment. [ABSTRACT FROM AUTHOR]