LncRNA AFAP1-AS1 mediates breast cancer cell proliferation and migration through the miR-21/PTEN axis.

LncRNAs play various effects, mostly by sponging with miRNAs. Based on public databases integrating bioinformatics analyses and further validation in breast cancer (BC) tissue and cell lines, the effect of lncRNA AFAP1-AS1 on breast cancer cell proliferation and migration was verified. It might work via the miR-21/PTEN axis. The expression of AFAP1-AS1, which was significantly upregulated in BC tissues and cell lines, was correlated with old age and lymph node metastasis of patients with BC. Knockdown of AFAP1-AS1 inhibited the proliferation and migration of BC cells in vitro and in vivo. And downregulated miR-21 expression and upregulated PTEN expression additionally. Mechanistically, the knockdown of lncRNA AFAP1-AS1 upregulated PTEN expression and consequently attenuated miR-21-mediated enhanced BC cell proliferation and migration. LncRNA AFAP1-AS1 is a potential prognostic biomarker for BC patients.

Actin filament-associated protein 1-antisense RNA1 promotes the development and invasion of tongue squamous cell carcinoma via the AFAP1-AS1/miR-133a-5p/ZIC2 axis.

BACKGROUND: The present study aimed to explore the biological role and underlying mechanism of the long non-coding RNA actin filament-associated protein 1-antisense RNA1 (lncRNA AFAP1-AS1) in the progression of tongue squamous cell carcinoma (TSCC). METHODS: A quantitative reverse transcriptase-PCR (RT-qPCR) was conducted to assess relative levels of the miR-133a-5p, lncRNAs AFAP1-AS1 and zinc finger family member 2 (ZIC2) in TSCC cell lines and specimens, whereas ZIC2 protein levels were measured using western blotting. After modifying the levels of expression of lncRNA AFP1-AS1, miR-133a-5p and ZIC2 using lentivirus or plasmid transfection, we examined AKT/epithelial-mesenchymal transition signaling pathway alterations, in vivo carcinogenesis of TSCC in nude mice and in vitro malignant phenotypes. A dual-luciferase reporter assay was conducted to confirm the targeting relationship between ZIC2 and miR-133a-5p, as well as between miR-133a-5p and lncRNA AFAP1-AS1. Based on The Cancer Genome Atlas (TCGA) database, we additionally validated AFP1-AS1. The potential biological pathway for AFP1-AS1 was investigated using gene set enrichment analysis (GSEA). We also evaluated the clinical diagnostic capacities of AFP1-AS1 and clustered the most potential biomarkers with the Mfuzz expression pattern. Finally, we also made relevant drug predictions for AFP1-AS1. RESULTS: In TSCC cell lines and specimens, lncRNA AFAP1-AS1 was upregulated. ZIC2 was upregulated in TSCC cells as a result of lncRNA AFAP1-AS1 overexpression, which also promoted TSCC cell migration, invasion, viability, and proliferation. Via the microRNA sponge effect, it was found that lncRNA AFAP1-AS1 could upregulate ZIC2 by competitively inhibiting miR-133a-5p. Interestingly, knockdown of ZIC2 reversed the biological roles of lncRNA AFAP1-AS1 with respect to inducing malignant phenotypes in TSCC cells. In addition, in vivo overexpression of lncRNA AFAP1-AS1 triggered subcutaneous tumor growth in nude mice implanted with TSCC cells and upregulated ZIC2 in the tumors. The TCGA database findings revealed that AFAP1-AS1 was significantly upregulated in TSCC specimens and had good clinical diagnostic value. The results of GSEA showed that peroxisome proliferator-activated receptor signaling pathway was significantly correlated with low expression of AFP1-AS1. Finally, the results of drug prediction indicated that the group with high AFAP1-AS1 expression was more sensitive to docetaxel, AZD4547, AZD7762 and nilotinib. CONCLUSIONS: The upregulation of lncRNA AFAP1-AS1, which increases TSCC cell viability, migration, proliferation and invasion via the AFAP1-AS1/miR-133a-5p/ZIC2 axis, aids in the progression of TSCC.

LncRNA AFAP1-AS1 regulates proliferation and apoptosis of endometriosis through activating STAT3/TGF-ß/Smad signaling via miR-424-5p.

AIM: Endometriosis is a common gynecological disorder characterized by chronic pelvic pain and infertility, which negatively affects women's health worldwide. AFAP1-AS1 has been implicated in endometriosis lesions recently, but its mechanism of endometriosis progression remains unclear. METHODS: Endometrial stromal cells (ESCs) were used to identify the role of AFAP1-AS1 in endometriosis. The migratory capability was determined by transwell. Gene and protein expressions were identified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability and apoptosis were detected by MTT assays and flow cytometry, respectively. Luciferase report assays were used to identify the interaction of AFAP1-AS1, miR-424-5p and signal transducer and activator of transcription 3 (STAT3). RESULTS: AFAP1-AS1 knockdown or miR-424-5p overexpression inhibited proliferation and migration, and promoted apoptosis in ESCs. In addition, knockdown of AFAP1-AS1 repressed the expression of ki-67 and Bcl-2, and promoted the levels of cleaved caspase-3 and Bax. Furthermore, knockdown of AFAP1-AS1 inhibited the conversion of E-cadherin to N-cadherin and the expression of Snail. Moreover, AFAP1-AS1 activated the STAT3/transforming growth factor-ß1 (TGF-ß1)/Smad2 axis via directly targeting miR-424-5p. The regulatory effect of AFAP1-AS1 silencing in ESC migration, proliferation, and apoptosis was reversed by miR-424-5p inhibition or STAT3 overexpression. CONCLUSIONS: AFAP1-AS1 silencing could inhibit cell proliferation and promote apoptosis by regulating STAT3/TGF-ß/Smad signaling pathway via targeting miR-424-5p in ESCs. AFAP1-AS1 may be a potential therapeutic target of controlling the progression of endometriosis.

Prognostic value of lncRNA AFAP1-AS1 in breast cancer: a meta-analysis and validated study in Chinese population.

BACKGROUND: Long non encoding RNA (lncRNA) plays a crucial role in breast cancer. However, the prognostic role of AFAP1-AS1 in breast cancer remains unclear. AIMS: To investigate the relationship between the expression of long non-coding RNA actin filament-associated protein1 antisense RNA1 (AFAP1-AS1) and prognosis of breast cancer. METHODS AND RESULTS: Meta-analysis was performed to explore the correlation between AFAP1-AS1 and breast cancer. The AFAP1-AS1expression in patients with breast cancer tissue and adjacent normal tissue from 153 patients was determined by qRT-PCR. Bioinformatics and Cox proportional-hazards risk model were used to explore the relationship between expression of AFAP1-AS1 and prognosis. The combined analysis revealed a significant correlation between AFAP1-AS1 expression and both overall survival (hazard ratios, HR = 2.33, 95%Cl: 1.94-2.81, p < 0.001) as well as disease-free survival/progression-free survival (HR = 2.94, 95%CI: 2.35-3.67, p < 0.001). The relation between expression of AFAP1-AS1 and breast cancer was determined in 153 breast cancer and adjacent normal tissues. The findings revealed a significantly higher AFAP1-AS1expression levels in breast cancer tissues compared to adjacent normal tissues (p < 0.001). Additionally, patients exhibiting heightened levels of AFAP1-AS1 expression were correlated with an unfavorable prognosis (HR = 2.35, 95%CI: 1.47-3.74, p < 0.001), which aligns consistently with the findings of the pooled analysis. The subgroup analysis of clinical characteristics revealed a significant association between high expression of AFAP1-AS1 and TNM stage (HR = 1.72, 95%CI: 1.11-2.65, p = 0.015). CONCLUSION: This study demonstrated that AFAP1-AS1 acts as an oncogene and may serve as a novel prognostic marker for breast cancer, particularly in the Chinese population.

Metformin suppresses lung adenocarcinoma by downregulating long non-coding RNA (lncRNA) AFAP1-AS1 and secreted phosphoprotein 1 (SPP1) while upregulating miR-3163.

AFAP1-AS1 plays a pro-tumor role in lung cancer. However, no investigation has focused on whether it is involved in the anticancer activity of metformin (Met) in the treatment of lung adenocarcinoma (LUAD). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression of long non-coding (lnc)RNA AFAP1-AS1, the microRNA (miR)-3163, and secreted phosphoprotein 1 (SPP1) in LUAD tissues, or of A549 and H3122 cells. Cell Counting Kit-8, wound scratch, and cell invasion assays were performed to evaluate the effect of the overexpression of lncRNA AFAP1-AS1, miR-3163, and SPP1 on the malignant behaviors of A549 and H3122 cells. Phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway-related proteins were detected by Western blot analysis. Dual luciferase reporter or RIP assays were used to determine the interplay between AFAP1-AS1 and miR-3163, or of miR-3163 and SPP1. Met inhibits the malignant characteristics of A549 and H3122 cells in vitro. GEPIA database analysis showed that AFAP1-AS1 is a highly expressed lncRNA in LUAD tissues, which was validated by RT-qPCR. Overexpression of AFAP1-AS1 suppressed the met-mediated anti-tumor activity in A549 and H3122 cells, while AFAP1-AS1 silencing promoted it. Met inhibited AFAP1-AS1 expression, which resulted in reduced proliferation, migration, and invasion in A549 and H3122 cells. This led to AFAP1-AS1-mediated suppression of miR-3163 and, subsequently, the upregulation of SPP1. Met exerts its antitumor activities by regulating the AFAP1-AS1/miR-3163/SPP1/PI3K/Akt/mTOR axis. Our findings deepen our understanding of mechanisms underlying anti-tumor effect of Met in LUAD.

Long non-coding ribonucleic acid AFAP1-AS1 promotes chondrocyte proliferation via the miR-512-3p/matrix metallopeptidase 13 (MMP-13) axis.

Long-chain non-coding RNAs are reported to be involved in cartilage damage. However, less research on the role of actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) in osteoarthritis. To investigate AFAP1-AS1 function in osteoarthritis development, AFAP1-AS1 and miR-512-3p expression levels in osteoarthritis cartilage and cells were evaluated using RT-qPCR. The downstream target genes of AFAP1-AS1 and miR-512-3p were predicted and validated using luciferase reporter assays. Moreover, a knee osteoarthritis model was established by injecting monoiodoacetate into the knee joints of mice. The effects of AFAP1-AS1 and miR-512-3p on osteoarthritis chondrocyte proliferation and MMP-13, collagen II, and collagen IV expressions were detected in vivo using CCK-8 assay and Western blotting and RT-qPCR, respectively. AFAP1-AS1 expression was upregulated in osteoarthritis cartilage and cells. MiR-512-3p expression was downregulated in osteoarthritis cartilage. AFAP1-AS1 overexpression inhibited miR-512-3p expression in chondrocytes. Furthermore, AFAP1-AS1 over-expression promoted chondrocyte proliferation, and miR-512-3p mimic inhibited chondrocyte proliferation in vivo. AFAP1-AS1 overexpression reduced type II and type IV collagen expression, while miR-512-3p overexpression promoted type II and type IV collagen in vivo. AFAP1-AS1 overexpression enhanced MMP-13 expression in vivo. AFAP1-AS1 overexpression regulated chondrocyte proliferation by inhibiting miR-512-3p expression in vivo. AFAP1-AS1 could be a potential target to treat osteoarthritis by inhibiting miR-512-3p and subsequently inducing chondrocyte proliferation and regulating matrix synthesis.

Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer.

This investigation attempted to discern whether formononetin restrained progression of triple-negative breast cancer (TNBC) by blocking lncRNA AFAP1-AS1-miR-195/miR-545 axis. We prepared TNBC cell lines (i.e. MDA-MB-231 and BT-549) and normal human mammary epithelial cell line (i.e. MCF-10A) in advance, and the TNBC cell lines were, respectively, transfected by pcDNA3.1-lncRNA AFAP1-AS1, si-lncRNA AFAP1-AS1, pcDNA6.2/GW/EmGFP-miR-545 or pcDNA6.2/GW/EmGFP-miR-195. Resistance of TNBC cells in response to 5-Fu, adriamycin, paclitaxel and cisplatin was evaluated through MTT assay, while potentials of TNBC cells in proliferation, migration and invasion were assessed via CCK8 assay and Transwell assay. Consequently, silencing of lncRNA AFAP1-AS1 impaired chemo-resistance, proliferation, migration and invasion of TNBC cells (P<0.05), and over-expression of miR-195 and miR-545, which were sponged and down-regulated by lncRNA AFAP1-AS1 (P<0.05), significantly reversed the promoting effect of pcDNA3.1-lncRNA AFAP1-AS1 on proliferation, migration, invasion and chemo-resistance of TNBC cells (P<0.05). Furthermore, CDK4 and Raf-1, essential biomarkers of TNBC progression, were, respectively, subjected to target and down-regulation of miR-545 and miR-195 (P<0.05), and they were promoted by pcDNA3.1-lncRNA AFAP1-AS1 at protein and mRNA levels (P<0.05). Additionally, formononetin significantly decreased expressions of lncRNA AFAP1-AS1, CDK4 and Raf-1, while raised miR-195 and miR-545 expressions in TNBC cells (P<0.05), and exposure to it dramatically contained malignant behaviors of TNBC cells (P<0.05). In conclusion, formononetin alleviated TNBC malignancy by suppressing lncRNA AFAP1-AS1-miR-195/miR-545 axis, suggesting that molecular targets combined with traditional Chinese medicine could yield significant clinical benefits in TNBC.

Silencing lncRNA AFAP1-AS1 Inhibits the Progression of Esophageal Squamous Cell Carcinoma Cells via Regulating the miR-498/VEGFA Axis.

PURPOSE: In view of the continuous increase of the mortality rate, esophageal squamous cell carcinoma (ESCC) develops into a major health concern. In this study, we aimed to investigate the underlying mechanism of long noncoding RNA (lncRNA) actin filament-associated protein 1 antisense RNA (AFAP1-AS1)/microRNA-498 (miR-498)/vascular endothelial growth factor A (VEGFA) in ESCC cells. METHODS: The expression levels of AFAP1-AS1, miR-498 and VEGFA in ESCC tissues and cells were detected using quantitative real-time polymerase chain reaction (qRT-PCR). The effects of AFAP1-AS1 on ESCC cells proliferation and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Transwell assay was carried out to determine cell migration. In addition, VEGFA and cell behaviors-related proteins were determined by Western blot analysis. The targeted relationships of AFAP1-AS1 were verified by dual-luciferase reporter and RNA pull-down assays. RESULTS: The expression levels of lncRNA AFAP1-AS1 and VEGFA mRNA were upregulated, but miR-498 was downregulated in ESCC tissues and cells. Moreover, miR-498 was directly targeted by AFAP1-AS1 and there was a negative correlation between miR-498 and AFAP1-AS1. Functionally, AFAP1-AS1 silencing inhibited the proliferation and migration and induced apoptosis of ESCC cells. Interestingly, miR-498 inhibition rescued the effects of AFAP1-AS1 knockdown on cell proliferation, apoptosis and migration and restored the expression levels of tumor-developing marker proteins of AFAP1-AS1 silencing in Eca109 and KYSE-30 cells. Furthermore, VEGFA was verified as a direct target of miR-498 and reversed the effects of miR-498 overexpression on cell behaviors of ESCC in vitro. CONCLUSION: Downregulation of AFAP1-AS1 impeded the proliferation and migration and induced apoptosis of ESCC cells by regulating miR-498/VEGFA axis, which might serve as a novel biomarker for the diagnosis and treatment of ESCC.

Bidirectional interaction of lncRNA AFAP1-AS1 and CRKL accelerates the proliferative and metastatic abilities of hepatocarcinoma cells.

Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long non-coding RNA transcribed from the antisense strand of protein coding gene AFAP1, has attracted attention in cancer research. Despite, its biological function and regulatory mechanism in hepatocellular carcinoma still unknown. The present study revealed AFAP1-AS1 mediated hepatocarcinoma progression through targeting CRKL. The bidirectional interaction of AFAP1-AS1 and oncogenic protein CRKL, and the deregulation of AFAP1-AS1 effects on Ras, MEK and c-Jun activities were investigated in depth. AFAP1-AS1 was upregulated in surgical tumorous tissues from hepatocarcinoma patients compared with the paired paracancerous non-tumor liver tissues, and in hepatocarcinoma Huh7, HCCLM3 and HepG2 cell lines compared with LO2, a normal liver cell line. AFAP1-AS1 knockdown noticeably suppressed the proliferative, migratory and invasive properties, and the epithelial-mesenchymal transition (EMT) process of HepG2 and HCCLM3 through upregulating E-cadherin and downregulating N-cadherin and vimentin. CRKL knockdown reduced AFAP1-AS1 expression levels in HepG2 and HCCLM3 cells. AFAP1-AS1 suppression impaired CRKL expression in HepG2 and HCCLM3. AFAP1-AS1 level change was positively correlated with the expression level changes of Ras, MEK and c-Jun in mediating the invasiveness of hepatocarcinoma cells. Current work demonstrated AFAP1-AS1 to be an applicable progression indicator of hepatocarcinoma. AFAP1-AS1 probably promotes the proliferation, EMT progression and metastasis of hepatocarcinoma cells via CRKL mediated Ras/MEK/c-Jun and cadherin/vimentin signaling pathways. AFAP1-AS1-CRKL bidirectional feedback signaling is worthy of further study on the monitoring, diagnosis and treatment of cancers.

Long Noncoding RNA AFAP1-AS1 Is a Critical Regulator of Nasopharyngeal Carcinoma Tumorigenicity.

BACKGROUND: The long noncoding RNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is a critical player in various cancers. However, the clinical value and functional mechanisms of AFAP1-AS1 during the tumorigenicity of nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the clinical application and potential molecular mechanisms of AFAP1-AS1 in NPC tumorigenesis and progression. METHODS: The expression level of AFAP1-AS1 was determined by qRT-PCR in 10 paired fresh human NPC tissues and adjacent normal tissues. RNAscope was performed on 100 paired paraffin-embedded NPC and adjacent nontumor specimens. The biological functions of AFAP1-AS1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays were performed to detect and identify the AFAP1-AS1-interacting protein KAT2B. Protein-RNA immunoprecipitation (RIP) assays were conducted to examine the interaction of AFAP1-AS1 and KAT2B. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of transcription intermediary factor 1 alpha (TIF1α) and H3K14ac on the RBM3 promoter. RESULTS: AFAP1-AS1 is upregulated in NPC and is a poor prognostic indicator for survival in NPC patients. AFAP1-AS1 was required for NPC proliferation in vitro and tumorigenicity in vivo. Mechanistic investigations suggested that AFAP1-AS1 binds to KAT2B and promotes acetyltransferase activation at two residues (E570/D610). KAT2B further promotes H3K14 acetylation and protein binding to the bromo domain of TIF1α. Consequently, TIF1α acts as a nuclear transcriptional coactivator of RBM3 transcription, leading to YAP mRNA stabilization and enhanced NPC tumorigenicity. CONCLUSIONS: Our findings suggest that AFAP1-AS1 functions as an oncogenic biomarker and promotes NPC tumorigenicity through enhanced KAT2B acetyltransferase activation and YAP mRNA stabilization.

Knockdown of Long Non-Coding RNA AFAP1-AS1 Promoted Viability and Suppressed Death of Cardiomyocytes in Response to I/R In Vitro and In Vivo.

Long non-coding RNA (lncRNA) plays a pivotal role in the development of myocardial infarction (MI). The aim of this study was to investigate the effects of lncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on cell cycle, proliferation, and apoptosis. RT-qPCR was used to detect the expression levels of AFAP1-AS1, miR-512-3p, and reticulon 3 (RTN3) in rat model of I/R. The simulated MI environment was constructed. MTT assay and flow cytometry were used to detect changes in cardiomyocyte viability and cell cycle/apoptosis after MI by AFAP1-AS1 silencing or RTN3 silencing. The targeting relationship of miR-512-3p and AFAP1-AS1 and RTN3 in cardiomyocytes was verified by dual luciferase reporter assay. The expression levels of AFAP1-AS1 and RTN3 were significantly upregulated in a rat model of LAD ligation (or MI) ligation, while the expression level of miR-512-3p was significantly reduced. Overexpressed AFAP1-AS1 and RTN3 promoted cardiomyocyte apoptosis and inhibited cardiomyocyte proliferation. MiR-512-3p was a direct target of AFAP1-AS1, and RTN3 was a direct target of miR-512-3p. AFAP1-AS1 promoted the progression of MI by targeting miR-512-3p. AFAP1-AS1 promoted the progression of MI by modulating the miR-512-3p/RTN3 axis. AFAP1-AS1 may be a potential therapy target for MI. Graphical Abstract The role of AFAP1-AS1 in regulating MI injury in vivo. (A) Effect of AFAP1-AS1 in MI injury in vivo. (B) The mRNA level of RTN3 in MI injury in vivo. (C) The protein level of RTN3 in MI injury in vivo. (D) Effect of miR-512-3p in MI model group. (E) TUNEL assay. *P < 0.05, **P < 0.01 vs the sham group; #P < 0.05, ##P < 0.01 vs the MI group.

M2 Macrophage-Derived Exosomal lncRNA AFAP1-AS1 and MicroRNA-26a Affect Cell Migration and Metastasis in Esophageal Cancer.

Exosomes from cancer cells or immune cells, carrying bio-macromolecules or long non-coding RNAs (lncRNAs), participate in tumor pathogenesis and progression by modulating the microenvironment. This study aims to explore the function of M2 macrophage-derived exosomes on the invasion and metastasis of esophageal cancer (EC) with the involvement of the lncRNA AFAP1-AS1/microRNA-26a (miR-26a)/activating transcription factor 2 (ATF2) axis. We found that lncRNA AFAP1-AS1 could specifically bind to miR-26a, thus affecting the expression of miR-26a, and ATF2 was the direct target of miR-26a. Compared with M1 macrophage-derived exosomes, M2 macrophage-derived exosomes exhibited higher AFAP1-AS1 and ATF2 expression and lower miR-26a expression. Moreover, extracellular AFAP1-AS1 could be moved to KYSE410 cells via being incorporated into M2 macrophage-derived exosomes. M2 macrophage-derived exosomes could downregulate miR-26a and promote the expression of ATF2 through high expression of AFAP1-AS1, thus promoting the migration, invasion, and lung metastasis of EC cells; M2-exosomes upregulating AFAP1-AS1 or downregulating miR-26a ameliorated this effect. In summary, M2 macrophage-derived exosomes transferred lncRNA AFAP1-AS1 to downregulate miR-26a and upregulate ATF2, thus promoting the invasion and metastasis of EC. Targeting M2 macrophages and the lncRNA AFAP1-AS1/miR-26a/ATF2 signaling axis represents a potential therapeutic strategy for EC.

LncRNA GAS8-AS inhibits colorectal cancer (CRC) cell proliferation by downregulating lncRNA AFAP1-AS1.

LncRNA GAS8-AS1 inhibits thyroid carcinoma, while its role in colorectal cancer (CRC) is unknown. In the present study we found that plasma GAS8-AS1 was upregulated in early stage CRC patients, and downregulation of GAS8-AS1 effectively distinguished CRC patients from healthy controls. LncRNA AFAP1-AS1 was upregulated in CRC patients and was inversely correlated with GAS8-AS1 only in CRC patients but not in healthy controls. GAS8-AS1 overexpression mediated the downregulation of AFAP1-AS1 in colon cancer cells, while AFAP1-AS1 overexpression did not significantly affect GAS8-AS1 expression. Expression level of GAS8-AS1 decreased, while expression level of AFAP1-AS1 increased with the increase of primary tumor diameters. GAS8-AS1 overexpression led to inhibited, while AFAP1-AS1 overexpression led to promoted proliferation of CRC cells, and AFAP1-AS1 overexpression reduced the inhibitory effects of GAS8-AS1 overexpression on cancer cell proliferation. Therefore, GAS8-AS may inhibit CRC cell proliferation by downregulating AFAP1-AS1.

The prognostic value of high LncRNA AFAP1-AS1 expression in various cancers: A systematic review and meta-analysis containing 21 studies.

BACKGROUNDS: Plenty of studies have been conducted to explore the prognostic value of LncRNA AFAP1-AS1 in various cancers, however, with contradictory outcomes. The aim of the current study was to explore the prognostic value of high LncRNA AFAP1-AS1 expression in various cancers. METHODS: PubMed, EMBASE, Web of Science, Cochrane library, China National Knowledge Internet (CNKI) and Wan-fang database were comprehensively retrieved, and all the relevant studies were included into the study. RESULTS: A total of 21 studies involving 2179 patients were finally included into the systematic review and meta-analysis. Compared to low LncRNA AFAP1-AS1 expression, high LncRNA AFAP1-AS1 expression was significantly related to shorter OS (HR = 2.02, 95%CI = 1.51-2.70, P < 0.001; I2 = 78%), DFS(HR = 1.80, 95%CI = 1.16-2.80, P = 0.009; I2 = 0%), RFS (HR = 2.90, 95%CI = 1.79-4.69, P < 0.001; I2 = 38%)and PFS(HR = 2.18, 95%CI = 1.62-2.92, P < 0.001; I2 = 0%) in patients with various cancers. Besides, high LncRNA AFAP1-AS1 expression was significantly associated with smoking (P < 0.001), advanced clinical stage (P < 0.001), larger tumor size (P < .001), earlier tumor metastasis (P < 0.001), earlier lymph nodal involvement (P = 0.002) and vascular invasion (P < 0.001) in various cancers. CONCLUSIONS: Cancer patients with high LncRNA AFAP1-AS1 expression had shorter OS, DFS, RFS and PFS compared to those with low expression. Moreover, high LncRNA AFAP1-AS1 expression was significantly related to advanced clinical stage, larger tumor size, earlier tumor metastasis, earlier lymph nodal involvement and vascular invasion. High LncRNA AFAP1-AS1 expression was an unfavorable prognostic factor in various cancers.

The long coding RNA AFAP1-AS1 promotes tumor cell growth and invasion in pancreatic cancer through upregulating the IGF1R oncogene via sequestration of miR-133a.

Long non-coding RNAs (lncRNAs) have been shown to play a significant role in the progression of many cancers, including pancreatic cancer (PC). However, the biological function and regulatory mechanisms of lncRNAs in PC remains largely unclear. The aim of this study was to identify and evaluate the potential functions of lncRNAs in PC and reveal the underlying mechanisms of their effects. Screening of published microarray data (GEO accession Nos. GSE16515 and GSE32688), revealed lncRNA AFAP1-AS1 to be one of the most upregulated lncRNAs in PC tissues. High expression of AFAP1-AS1 was correlated with advanced stages, tumor size and lymph node metastasis, as well as with poorer overall survival in patients with PC. Functionally, knockdown of AFAP1-AS1 by transfection with siRNA inhibited the proliferative and invasive capacities of PaCa-2 and SW1990 PC cells, promoted apoptosis of PC cells in vitro, and impaired in-vivo tumorigenicity. In particular, it was hypothesized that AFAP1-AS1 may act as a competitive endogenous RNA (ceRNA), effectively becoming a sink for miR-133a whose expression was found to be downregulated in PC tissues and cell lines, and which was negatively correlated with the expression of AFAP1-AS1. We also found that the IGF1R oncogene which is an important regulator of MEK/ERK signaling pathway, was positively regulated by AFAP1-AS1 through ameliorating miR-133a-mediated IGF1R repression in PC tissues. Moreover, we demonstrated that knockdown of IGF1R by transfection with si-IGF1R suppressed cell proliferation, invasion and migration of PaCa-2 and SW1990 PC cells, suggesting that IGF1R may function as an oncogene in PC cells. Further investigations revealed that miR-133a reversed the biological effects of AFAP1-AS1 on PC cells. Collectively, the findings provide new evidence that AFAP1-AS1 could regulate the progression of pancreatic cancer by acting as a ceRNA, and suggest it has potential for use as both a biomarker for the early detection PC and for the development of individualized therapies for PC.

Overexpression of LncRNA AFAP1-AS1 predicts poor prognosis and promotes cells proliferation and invasion in gallbladder cancer.

BACKGROUND: Long non-coding RNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been elucidated to be associated with some kinds of human cancers. However, whether lncRNA AFAP1-AS1 implicates in tumor development of gallbladder cancer (GBC) remains largely unknown. This study aims to elucidate the tumorigenic role and regulatory function of lncRNA AFAP1-AS1 in gallbladder cancer. METHODS: We analyzed lncRNA AFAP1-AS1 expression by quantitative real time PCR (qRT-PCR) in 40 gallbladder cancer tissue and adjacent normal tissues, survival plots were generated by Kaplan-Meier analysis and the log-rank test. The expression levels of transcription factor Twist1 and epithelial-to mesenchymal transition (EMT) makers (E-cadherin and Vimentin) were detected by quantitative real time PCR and western blotting analysis after knockdown of lncRNA AFAP1-AS1. RESULTS: The expression levels of lncRNA AFAP1-AS1 were significantly elevated in GBC tissues and GBC cell lines. In addition, the expression level of lncRNA AFAP1-AS1 was significantly associated with tumor sizes and the higher expression of lncRNA AFAP1-AS1 was correlated with poor prognosis in GBC patients. Knockdown of LncRNA AFAP1-AS1 suppressed cell growth and invasion in NOZ and GBC-SD cells. Furthermore, we found that knockdown of LncRNA AFAP1-AS1 in GBC cells inhibited EMT by down-regulating the transcription factor Twist1 and Vimentin and up-regulated the E-cadherin. CONCLUSIONS: Our results suggested lncRNA AFAP1-AS1 was correlated with poor prognosis in GBC patients and lncRNA AFAP1-AS1 might be novel therapeutic target in gallbladder cancer.

The up-regulation of long non-coding RNA AFAP1-AS1 is associated with the poor prognosis of NSCLC patients.

Long non-coding RNA (lncRNA) is actively transcribed from human genome and has been considered to participate in many processes of various cancers. The purpose of this study was to investigate the expression of LncRNA AFAP1-AS1 and its prognostic value in NSCLC. LncRNA AFAP1-AS1 expression was detected by qRT-PCR which demonstrated that the expression was significantly increased in tumor tissues compared with the adjacent non-cancerous tissues and healthy tissues. The clinical stage, smoking history, infiltration degree, lymph node metastasis and distant metastasis were all proved to impact the expression of LncRNA AFAP1-AS1 (P<0.05). Kaplan-Meier analysis was performed to evaluate the overall survival of NSCLC patients with different expression level of LncRNA AFAP1-AS1, and results showed that patients with high LncRNA AFAP1-AS1 expression lived shorter than those with low LncRNA AFAP1-AS1 expression (Log rank test, P<0.001). Besides, the prognostic value of LncRNA AFAP1-AS1 as well as the clinical features was assessed by Cox regression analysis. The outcome revealed that LncRNA AFAP1-AS1 was closely related to the prognosis of NSCLC. Taken together, LncRNA AFAP1-AS1 was up-regulated in NSCLC tissues and it could be an independent prognostic indicator for NSCLC patients.