Accumulating studies have implicated the role of long non-coding RNAs (lncRNAs) in the pathogenesis of hepatocellular carcinoma (HCC) through the regulating transcription and mRNA stability. A recent report has linked Rac GTPase-activating protein 1 (RACGAP1) to the early recurrence of HCC. The current study aimed to ascertain whether MAGI2 antisense RNA 3 (MAGI2-AS3) influences the development of HCC by regulating RACGAP1. MAGI2-AS3 expression was initially quantified in both the HCC tissues and cell lines. In order to elucidate the role of MAGI2-AS3 in the development of HCC, MAGI2-AS3 was overexpressed or silenced in HCC cells after which cell proliferation, apoptosis, invasion, and migration were evaluated. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and biotin-labeled RNA pull-down assays were conducted to determine the interactions among MAGI2-AS3, KDM1A, and RACGAP1. Finally, the effects of MAGI2-AS3 and RACGAP1 on the tumorigenesis of transplanted HCC cells in nude mice were evaluated. MAGI2-AS3 was found to be under-expressed in HCC tissues and cell lines. The restoration of MAGI2-AS3 was identified to markedly inhibit HCC cell growth, migrating ability, and invasiveness, and promote cell apoptosis. Interaction between MAGI2-AS3 and KDM1A was identified. KDM1A recruited by MAGI2-AS3 was found to promote H3K4me2 demethylation at the RACGAP1 promoter, which ultimately decreased the expression of RACGAP1. We also identified that RACGAP1 knockdown eliminated the stimulatory effects of MAGI2-AS3 silencing on the malignant phenotypes of HCC cells. Additionally, the expression of MAGI2-AS3 reduced tumor weight and size in HCC transplanted nude mice. Taken together, the key observations of the current study demonstrate the potential of MAGI2-AS3 as a tumor suppressor and a promising target for HCC treatment.

Introduction. The biological roles of microRNA-654-5p (miR-654-5p) in cancers have been previously reported. However, its role in colorectal cancer (CRC) remains largely unknown. The purpose of this work was to investigate the roles and associated mechanisms in CRC. Methods. Quantitative Real-Time PCR (qRT-PCR) was utilized to explore the expression pattern of miR-654-5p in CRC cells. Cell Counting Kit-8 (CCK-8) assay, wound-healing assay, and transwell invasion assay were conducted to investigate the effects of miR-654-5p on CRC cell proliferation, migration, and invasion, respectively. Moreover, the mechanisms behind miR-654-5p regulates CRC progression were investigated. Results. Compared with normal cell line, miR-654-5p expression level was significantly suppressed in CRC cells. After overexpression of miR-654-5p, the malignancy behaviors of CRC cells including cell proliferation, migration, and invasion were remarkably decreased. Subsequently, we found hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) was a putative target for miR-654-5p. Rescue experiments showed overexpression of HAX-1 could partially reversed the effects of miR-654-4p on CRC cell events. Conclusion. miR-654-5p was reduced expression in CRC cells and could regulate CRC progression via targeting HAX-1.

Introduction In East Asia, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer types. Long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 ( PART1 ) was reported to play crucial roles in regulating cancer progression. However, roles and mechanisms of action of PART1 in hepatocellular carcinoma (HCC) still remain unknown. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) method was used to detect the PART1 expression level in HCC cells. Cell proliferation, colony formation, and transwell invasion assays were performed to investigate the biological roles of PART1 on HCC cell behaviors. Bioinformatic analysis methods were performed to analyze connections of microRNA-590-3p (miR-590-3p) with PART1 or high mobility group box 2 ( HMGB2 ) in HCC. Moreover, expression levels of PART1 , miR-590-3p, and HMGB2 in HCC tissues and normal tissues were analyzed at ENCORI. Results PART1 expression was found to be significantly upregulated in HCC tissues and cells. Functionally, silencing of PART1 significantly suppressed HCC cell proliferation, colony formation and invasion in vitro, while forcing PART1 exerts opposite biological effects. Mechanically, miR-590-3p/ HMGB2 axis was downstream target of PART1 , and silencing of miR-590-3p or forcing of HMGB2 could rescue the stimulation effects of PART1 overexpression on HCC cell behaviors. Discussion Our results provided evidence that PART1 serves as oncogenic lncRNA through sponging miR-590-3p to upregulate HMGB2 expression in HCC.

In this study, we determined the involvement of SOX2 and its downstream signaling molecules in hepatocellular carcinoma (HCC) progression. We carried out lentiviral transfection in HepG2 cells to determine the roles of SOX2, CCAT1, EGFR, miR-222-5p, and CYLD in HepG2 cells. We first determined the interaction between SOX2 and CCAT1 and that between miR-222-5p and CYLD and their effect on tumor growth in vivo was analyzed in HCC-xenograft bearing nude mice xenografts. SOX2 and CCAT1 were highly expressed in HCC tissues and HepG2 cells. SOX2 bound to the regulatory site of CCAT1. Silencing of SOX2 or CCAT1 inhibited HepG2 cell proliferation, migration, and invasion as well as decreased the expression of CCAT1 and EGFR. CCAT1 silencing reduced EGFR expression, but EGFR expression was increased in HCC tissues and HepG2 cells, which promoted proliferation, migration, and invasion in vitro . EGFR upregulated miR-222-5p, leading to downregulation of CYLD. miR-222-5p inhibition or CYLD overexpression repressed cell functions in HepG2 cells. SOX2 silencing decreased CCAT1, EGFR, and miR-222-5p expression but increased CYLD expression. Loss of SOX2 also reduced the growth rate of tumor xenografts. In summary, SOX2-mediated HCC progression through an axis involving CCAT1, EGFR, and miR-222-5p upregulation and CYLD downregulation.

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