SH3PXD2A-AS1/miR-330-5p/UBA2 ceRNA network mediates the progression of colorectal cancer through regulating the activity of the Wnt/β-catenin signaling pathway.

Long non-coding RNAs have important roles in the occurrence and progression of various cancers. However, the molecular mechanism of lncRNAs in colorectal cancer (CRC) is not well illustrated. Thus, we used bioinformatics methods to find potential lncRNAs associated with CRC progression, and chose SH3PXD2A-AS1 as a candidate for further analysis. The roles of SH3PXD2A-AS1 in CRC cells were determined by CCK-8, transwell invasion, wound healing and flow cytometry assays. Besides, we established the CRC tumor models in nude mice to study the effect of SH3PXD2A-AS1 on the tumor growth. Based on the ceRNA hypothesis, we used miRDB and miRTarBase websites to identify the SH3PXD2A-AS1-related ceRNA regulatory network, and measured the roles of this network in CRC cells. The results revealed that the expression profiles of SH3PXD2A-AS1 from GEO and TCGA databases showed an aberrant high level in CRC tissues compared with colorectal normal tissues. SH3PXD2A-AS1 over-expression was also found in CRC cells. SH3PXD2A-AS1 knockdown inhibited the CRC cellular proliferation, invasion and migration but induced apoptosis. Besides, SH3PXD2A-AS1 knockdown also suppressed the growth of CRC tumors. Furthermore, SH3PXD2A-AS1 could function as a ceRNA of miR-330-5p. Additionally, UBA2 was proved to be a target gene of miR-330-5p. Moreover, SH3PXD2A-AS1 knockdown downregulated UBA2 expression through sponging miR-330-5p to inactivate the Wnt/β-catenin signaling pathway, thereby inhibiting the cell growth and promoting apoptosis. Therefore, the SH3PXD2A-AS1/miR-330-5p/UBA2 network could regulate the progression of CRC through the Wnt/β-catenin pathway. These findings offer new sights for understanding the pathogenesis of CRC and provide potential biomarkers for CRC treatment.

Guo S ，Zhu KX ，Yu WH ，Wang T ，Li S ，Wang YX ，Zhang CC ，Guo JQ ... -  《-》

Long Non-Coding RNA SH3PXD2A-AS1 Promotes Cell Progression Partly Through Epigenetic Silencing P57 and KLF2 in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies worldwide. Current evidence has revealed the key roles of long non-coding RNAs (IncRNAs) in multiple cancers, including CRC. In this study we identified the lncRNA SH3PXD2A-AS1 as a novel molecule associated with CRC progression by analyzing the publicly available data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed to examine the expression levels of SH3PXD2A-AS1 in CRC tissue samples and CRC cell lines. Cell viability examination, colony-formation experiments, ethynyl deoxyuridine (Edu) assays and flow cytometry were performed to investigate the roles of SH3PXD2A-AS1 in CRC proliferation, cell cycle regulation, and apoptosis. Transwell assays were used to explore the effects of SH3PXD2A-AS1 on CRC cells migration and invasion. A nude mice model was used to assess the effects of SH3PXD2A-AS1 on tumorigenesis in vivo. Subcellular fractionation, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays were conducted to detect the molecular mechanisms of SH3PXD2A-ASl-mediated gene expression. Rescue assays were used to determine whether P57 and Kruppel-like factor 2 (KLF2) were involved in SH3PXD2A-ASl-dependent CRC proliferation. We firstly found that SH3PXD2A-AS1 was significantly upregulated in CRC tissues and cell lines, and overexpression of SH3PXD2A-AS1 was correlated with tumor size, TNM stage, and lymph node metastasis in patients with CRC. Furthermore, SH3PXD2A-AS1 knockdown inhibited CRC cells proliferation, migration and invasion in vitro, and suppressed tumorigenesis in vivo. Mechanistic studies indicated that SH3PXD2A-AS1 could epiqenetically repress P57 and KLF2 expression through interaction with EZH2. Rescue experiments suggested that SH3PXD2A-ASl-mediated oncogenesis was impaired by overexpression of P57 or KLF2. Interestingly, the expression of SH3PXD2A-AS1 was inversely correlated with the expression of P57 and KLF2 in CRC tissue samples. Our research presents the first evidence that SH3PXD2A-AS1 acts as an oncogene in CRC, and may be a promising diagnostic or therapeutic target in patients with CRC.

Ma Z ，Peng P ，Zhou J ，Hui B ，Ji H ，Wang J ，Wang K ... -  《-》

FGD5-AS1 facilitates glioblastoma progression by activation of Wnt/β-catenin signaling via regulating miR-129-5p/HNRNPK axis.

Accumulating evidence elucidates the biological significance of long non-coding RNA (lncRNAs) in tumorigenesis and development. FGD5 antisense RNA 1 (FGD5-AS1) was previously revealed as an oncogene in several types of malignancies. However, the roles of FGD5-AS1 in glioblastoma (GBM) and its potential molecular mechanisms remain unclear. The expression of FGD5-AS1, miR-129-5p, and heterogeneous nuclear ribonucleoprotein K (HNRNPK) mRNA were measured by qRT-PCR. Cell proliferation, invasion and apoptosis were determined by MTT, colony formation, transwell and flow cytometry assays. The protein levels of Ki-67, HNRNPK and Wnt signaling-associated genes were examined by western blot assay. The possible action mechanism of FGD5-AS1 was detected by bioinformatic tools, luciferase reporter, RIP and TOP/FOP Flash reporter assays. A nude mouse xenograft model was built to analyze the function of FGD5-AS1 in vivo. FGD5-AS1 expression was increased in GBM tumor tissues and cells. Knockdown of FGD5-AS1 inhibited cell proliferation and invasion in vitro, and slowed tumor growth in vivo. Mechanistically, FGD5-AS1 served as a sponge of miR-129-5p to relieve its suppression on HNRNPK. Moreover, down-regulation of HNRNPK repressed cell proliferation and invasion, while enhanced apoptosis. Additionally, si-FGD5-AS1-mediated suppression of cell proliferation and invasion was obviously reversed by the decrease of miR-129-5p or restoration of HNRNPK. Furthermore, FGD5-AS1 promoted cell growth and invasion by stimulating Wnt/β-catenin signaling via regulation of miR-129-5p/HNRNPK. FGD5-AS1 promoted GBM progression at least partly by regulating miR-129-5p/HNRNPK to activate Wnt/β-catenin signaling, suggesting the potential of FGD5-AS1 as a candidate target to improve GBM therapy.

Wu L ，Zhu X ，Song Z ，Guo M ，Liang J ，Yan D ... -  《-》

The lncRNA ZEB1-AS1 sponges miR-181a-5p to promote colorectal cancer cell proliferation by regulating Wnt/β-catenin signaling.

Lv SY ，Shan TD ，Pan XT ，Tian ZB ，Liu XS ，Liu FG ，Sun XG ，Xue HG ，Li XH ，Han Y ，Sun LJ ，Chen L ，Zhang LY ... -  《-》

Non-coding RNA MFI2-AS1 promotes colorectal cancer cell proliferation, migration and invasion through miR-574-5p/MYCBP axis.

Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play essential roles in the tumour progression. LncRNAs mostly act as competing endogenous RNAs (ceRNAs) by sponging miRNAs. This study aimed to study the association of a novel lncRNA MFI2-AS1 with miR-574-5p/MYCBP axis in the development of colorectal cancer (CRC). Ninety-four CRC tissues and paired adjacent non-tumour tissues were included in our study. The relative expression level of MFI2-AS1 was detected, and its relationship with clinico-pathological factors was analysed. Then, the CRC cells lines (LoVo and RKO) were transfected with MFI2-AS1 siRNA, miR-574-5p mimics and inhibitors. Cell proliferation, migration, invasion, cell cycle distribution and DNA damage in response to different transfection conditions were examined. Dual-luciferase reporter assay was performed to identify the target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP. LncRNA MFI2-AS1 and MYCBP were up-regulated in CRC tissues when compared with adjacent non-tumour tissues. The expression levels of MFI2-AS1 were significantly associated with tumour histological grade, lymph and distant metastasis, TNM stage and vascular invasion. Both MFI2-AS1 siRNA and miR-574-5p mimics inhibited proliferation, migration and invasion in LoVo and RKO cells. The transfection of miR-574-5p inhibitor showed MFI2-AS1 siRNA-induced changes in CRC cells. Dual-luciferase reporter assay revealed target interactions between MFI2-AS1 and miR-574-5p, miR-574-5p and MYCBP. These findings suggested that lncRNA MFI2-AS1 and MYCBP have promoting effects in CRC tissues. LncRNA MFI2-AS1 promoted CRC cell proliferation, migration and invasion through activating MYCBP and by sponging miR-574-5p.

Li C ，Tan F ，Pei Q ，Zhou Z ，Zhou Y ，Zhang L ，Wang D ，Pei H ... -  《-》