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Circular RNAs (circRNAs) function as essential regulators in diverse human cancers, including hepatocellular carcinoma (HCC). However, the function of circ_0000517 in HCC was unknown. We aimed to explore the roles and mechanisms of circ_0000517 in HCC. The levels of circ_0000517, RPPH1 mRNA and microRNA-1296-5p (miR-1296-5p) were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The characteristics of circ_0000517 were explored by RNase R digestion and actinomycin D assays. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell cycle process and cell apoptosis were analyzed by flow cytometry analysis. The function of circ_0000517 in vivo was explored by a murine xenograft model. The association between miR-1296-5p and circ_0000517 or thioredoxin domain containing 5 (TXNDC5) was determined by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The protein level of TXNDC5 was detected by Western blot assay. Circ_0000517 was upregulated in HCC tissues and cells. Silencing of circ_0000517 suppressed HCC cell viability and colony formation and promoted cell cycle arrest and apoptosis in vitro and hampered tumor growth in vivo. MiR-1296-5p was a target of circ_0000517 and the effects of circ_0000517 silencing on HCC cell viability, cell cycle, colony formation and apoptosis were abolished by miR-1296-5p inhibition. TXNDC5 functioned as a target gene of miR-1296-5p, and the inhibitory effect of miR-1296-5p on HCC cell progression was rescued by TXNDC5 overexpression. Moreover, circ_0000517 promoted TXNDC5 expression via targeting miR-1296-5p. Circ_0000517 accelerated HCC progression by upregulating TXNDC5 through sponging miR-1296-5p.

Background Long non-coding RNAs (lncRNAs) are essential regulators of tumorigenesis and the development of colorectal cancer (CRC). Here, we aimed to investigate the role of lncRNA GAS6-AS1 in CRC and its potential mechanisms. Methods Bioinformatics analyses evaluated the level of GAS6-AS1 in colon cancer, its correlation with clinicopathological factors, survival curve and diagnostic value. qRT-PCR were performed to detect the GAS6-AS1 level in CRC samples and cell lines. The CCK8, EdU, scratch healing, transwell assays and animal experiments were conducted to investigate the function of GAS6-AS1 in CRC. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene analyses were carried out to reveal interaction between GAS6-AS1, TRIM14, FUS, and miR-370-3p/miR-1296-5p. Results GAS6-AS1 was greatly elevated in CRC and positively associated with unfavorable prognosis of CRC patients. Functionally, GAS6-AS1 positively regulates CRC proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and induces CRC growth and metastasis in vivo. Moreover, GAS6-AS1 exerted oncogenic function by competitively binding to miR-370-3p and miR-1296-5p, thereby upregulating TRIM14. Furthermore, we verified that GAS6-AS1 and TRIM14 both interact with FUS and that GAS6-AS1 stabilized TRIM14 mRNA by recruiting FUS. Besides, rescue experiments furtherly demonstrated that GAS6-AS1 facilitate progression of CRC by regulating TRIM14. Conclusion Collectively, these findings demonstrate that GAS6-AS1 promotes TRIM14-mediated cell proliferation, migration, invasion, and EMT of CRC via ceRNA network and FUS-dependent manner, suggesting that GAS6-AS1 could be utilized as a novel biomarker and therapeutic target for CRC.

Background: Circular RNAs (circRNAs) function as essential regulators in diverse human cancers, including hepatocellular carcinoma (HCC). However, the function of circ_0000517 in HCC was unknown. We aimed to explore the roles and mechanisms of circ_0000517 in HCC. Materials and Methods: The levels of circ_0000517, RPPH1 mRNA andmicroRNA-1296-5p (miR-1296-5p) were measured using quantitative real-time polymerase chain reaction (qRT-PCR). The characteristics of circ_0000517 were explored by RNase R digestion and actinomycin D assays. Cell proliferation was evaluated by Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell cycle process and cell apoptosis were analyzed by flow cytometry analysis. The function of circ_0000517 in vivo was explored by a murine xenograft model. The association between miR-1296-5p and circ_0000517 or thioredoxin domain containing 5 (TXNDC5) was determined by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The protein level of TXNDC5 was detected by Western blot assay. Results: Circ_0000517 was upregulated in HCC tissues and cells. Silencing of circ_0000517 suppressed HCC cell viability and colony formation and promoted cell cycle arrest and apoptosis in vitro and hampered tumor growth in vivo. MiR-1296-5p was a target of circ_0000517 and the effects of circ_0000517 silencing on HCC cell viability, cell cycle, colony formation and apoptosis were abolished by miR-1296-5p inhibition. TXNDC5 functioned as a target gene of miR-1296-5p, and the inhibitory effect of miR-1296-5p on HCC cell progression was rescued by TXNDC5 overexpression. Moreover, circ_0000517 promoted TXNDC5 expression via targeting miR-1296-5p. Conclusion: Circ_0000517 accelerated HCC progression by upregulating TXNDC5 through sponging miR-1296-5p. Keywords: HCC, circ_0000517, miR-1296-5p, TXNDC5

Background The effect of circular RNAs (circRNAs) is widely studied in various human cancers, including breast cancer (BC). Herein, circUSPL1 has been recognized as a new regulator for BC progression. However, the detailed biological function and molecular mechanism of circUSPL1 in BC remain vague. Methods The expression level of circUSPL1, miR‐1296‐5p and metastasis associated 1 (MTA1) was examined by quantitative reverse transcription PCR. BC cell proliferation, migration, invasion, apoptosis and aerobic glycolysis were analyzed by colony formation assay, 5‐ethynyl‐2′‐deoxyuridine assay, wound healing assay, transwell assay, flow cytometry and glycolysis corresponding kits, respectively. The protein level of Bcl‐2, Bax, HK2, GLUT1 and MTA1 was evaluated by western blot analysis. The relationship of miR‐1296‐5p and circUSPL1 or MTA1 was affirmed using dual‐luciferase reporter or RIP assays. A murine xenograft model was conducted to analyze the tumor growth in vivo. Results CircUSPL1 and MTA1 expression level was increased, but miR‐1296‐5p was particularly reduced in BC tissues and cells. CircUSPL1 deficiency significantly inhibited BC cell proliferation, migration, invasion, glycolysis, and promoted cell apoptosis. In addition, circUSPL1 directly targeted miR‐1296‐5p, and downregulation of miR‐1296‐5p eliminated the inhibitory action of circUSPL1 knockdown. Additionally, overexpression of miR‐1296‐5p repressed cell malignant properties, while the suppressive effects were overturned by MTA1 elevation. Lastly, silencing of circUSPL1 inhibited tumor growth by sponging miR‐1296‐5p and regulating MTA1. Conclusion CircUSPL1 deficiency repressed BC cell malignant phenotypes through reducing MTA1 via targeting miR‐1296‐5p, which might provide a theoretical basis for BC treatment. CircUSPL1 acts as sponge for miR‐1296‐5p to upregulate MTA1 expression, thereby promoting breast cancer cell proliferation, migration, invasion, glycolysis and suppressing apoptosis in vitro, as well as impeding tumor growth in vivo.

Background The tumor suppressive role of miR-1296 is observed in triple negative breast cancer (TNBC). However, the effect of miR-1296-5p in ERBB2-positive breast cancers remains obscure. Methods Whether ERBB2 was the target gene of the miR-1296-5p was predicted by online software, and determined by dual-luciferase activity assay. miR-1296-5p expression levels were determined in breast cancer samples (114 breast cancer tissues and 30 adjacent normal tissues) by using qRT-PCR. The effect of miR-1296-5p and inhibition of ERBB2/mTORC1 signaling on the downstream target was assessed by Western blot. SK-BR-3 and BT-474 breast cancer cell line was transfected with miR-1296-5p mimic after which cell proliferation and apoptosis were determined by the clonogenic assay and the flow cytometry system, respectively. In addition, the chemotherapeutic drug sensitivity of SK-BR-3 and BT-474 cells transfected with miR-1296-5p mimic were determined by MTT assay. Results The luciferase assay carrying ERBB2 3′-untranslated region-based reporters expressed in SK-BR-3 and BT-474 cells suggested that ERBB2 was the target gene of miR-1296-5p. MiR-1296-5p was significantly decreased in breast cancer tissues compared to adjacent normal tissues. Moreover, it was declined in ERBB2-positive breast cancer samples compared with that in ERBB2-negative breast cancer tissues. Overexpressed miR-1296-5p reduced its target protein level and mTORC1/S6 activation, inhibited the proliferation of ERBB2-positive breast cancer cells and sensitized these cells to cisplatin and 5-fluorouracil-induced apoptosis. Conclusions Our findings suggest that miR-1296-5p is involved in the regulation of proliferation in breast cancer cells via targeting ERBB2/mTORC1 signaling pathway.

Hypoxia affects the advancement, metastasis, and metabolism of breast cancer (BC). The circular RNA ribonuclease P RNA component H1 (circRPPH1) (has_circ_0000515) is implicated in tumor progression. Nevertheless, the regulatory mechanism related to circRPPH1 in hypoxia-mediated triple-negative breast cancer (TNBC) progression is indistinct. The expression levels of circRPPH1, miR-1296-5p, tripartite motif-containing 14 (TRIM14) mRNA in tissue samples and cells were examined through quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, migration, and invasion were determined with Cell Counting Kit-8 (CCK-8) or transwell assays. The levels of glucose consumption and lactate production were assessed via the Glucose Assay Kit or Lactate Assay Kit. The protein levels of TRIM14, Glucose Transporter GLUT1 (GLUT1), and lactic dehydrogenase A (LDHA) were detected by western blot analysis. The targeting relationship between circRPPH1 or TRIM14 and miR-1296-5p was verified with dual-luciferase reporter assay. The role of circRPPH1 was confirmed via xenograft assay. We verified that circRPPH1 and TRIM14 expression were increased while miR-1296-5p expression was decreased in BC tissues and hypoxia-cultured TNBC cells. Functionally, circRPPH1 silencing reversed the promoting effect of hypoxia on viability, migration, invasion, and glycolysis of TNBC cells. CircRPPH1 knockdown repressed decreased TNBC cell growth in vivo. Mechanistically, circRPPH1 sponged miR-1296-5p to modulate TRIM14 expression. Also, miR-1296- 5p silencing restored circRPPH1 inhibition-mediated influence on the viability, migration, invasion, and glycolysis of hypoxia-treated TNBC cells. TRIM14 elevation overturned the inhibitory impact of miR-1296-5p mimic on viability, migration, invasion, and glycolysis of hypoxia-cultured TNBC cells. In conclusion, hypoxia-induced circRPPH1 fostered TNBC progression through regulation of the miR-1296-5p/TRIM14 axis, indicating that circRPPH1 was a promising target for TNBC treatment.