Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis.

Prostate cancer (PCa) is a commonly diagnosed malignant cancer and is the second- highest cause of cancer death in men worldwide. Enzalutamide is the second-generation inhibitor of androgen receptor signaling and is the fundamental drug for the treatment of advanced PCa. However, the disease will eventually progress to metastatic castration-resistant prostate cancer (CRPC) and aggressive neuroendocrine prostate cancer (NEPC) because of androgen-deprivation therapy (ADT) resistance. The aim of the study was to investigate the role of long non-coding RNA (lncRNA) AFAP1-AS1 in ADT resistance. Quantitative real-time PCR analysis (qPCR) was used to assess the expression of AFAP1-AS1 in PCa cell lines and tissues. Cell proliferation and invasion were assessed after AFAP1-AS1 knockdown using Cell Counting Kit (CCK)-8 and Transwell assay, respectively. A dual-luciferase reporter gene assay was carried out to validate the regulatory relationship among AFAP1-AS1, microRNA (miR)-15b, and insulin-like growth factor1 receptor (IGF1R). AFAP1-AS1 level was markedly increased in castration-resistant C4-2 cells and NE-like cells (PC3, DU145, and NCI-H660), compared with androgen-sensitive LNCaP cells. Enzalutamide treatment increased the expression of AFAP1-AS1 in vitro and in vivo. Functionally, AFAP1-AS1 knockdown repressed tumor cell proliferation and invasion. Mechanistically, AFAP1-AS1 functioned as an oncogene in PCa through binding to miR-15b and destroying its tumor suppressor function. Finally, we identified that AFAP1-AS1 up-regulated IGF1R expression by competitively binding to miR-15b to de-repress IGF1R. AFAP1-AS1 facilitates PCa progression by regulating miR-15b/IGF1R axis, indicating that AFAP1-AS1 may serve as a diagnostic biomarker and therapeutic target for PCa.

Liu B ，Jiang HY ，Yuan T ，Zhou WD ，Xiang ZD ，Jiang QQ ，Wu DL ... -  《-》

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.

Chen B ，Li Q ，Zhou Y ，Wang X ，Zhang Q ，Wang Y ，Zhuang H ，Jiang X ，Xiong W ... -  《-》

Long non-coding RNA AFAP1-AS1 promotes proliferation and invasion in prostate cancer via targeting miR-512-3p.

In the development of tumor therapy, the role of long non-coding RNA actin filagenin 1 antisense RNA 1 (1ncRNA AFAP1-AS1) is quite significant, but the actual role of AFAP1-AS1 in the treatment of prostate cancer has not been determined. In view of this, the author took AFAP1-AS1 as the research object to design an experimental study, and conducted an in-depth exploration of the pathogenesis of prostate cancer. RT-qPCR was used to detect the expression of AFAP1-AS1 and miR-512-3p in prostate cancer tissues and cell lines. Perforation, flow cytometry and CCK-8 were used to detect the effects of cell proliferation, migration and invasion of mir-512-3p and a AFAP1-AS1. And the luciferase reporter gene was used to detect the downstream target gene of AFAP1-AS1, and the expression of CDK4, CDK6 and CCND1 protein was detected by Western blot. AFAP1-AS1 is highly expressed in prostate cancer tissues and cell lines. The expression level of AFAP1-AS1 is correlated with histological grade and distant metastasis. The overall level of patients with high expression of AFAP1-AS1 is low, and their survival rate is relatively low. Silencing AFAP1-AS1 can significantly increase the proliferation and migration of prostate cancer cells. AFAP1-AS1 silencing induces cell cycle arrest at G0/G1 phase. The downstream target of AFAP1-AS1 was mir-512-3p. The role of AFAP1-AS1 in the progression of prostate cancer cells was mediated by mir-512-3p. AFAP1-AS1 regulates miR-512-3p, so as to realize the regulation effect on the proliferation, invasion and migration of prostate cancer cells, and thereby promote the occurrence and development of prostate cancer, so as to provide the corresponding program for the treatment of prostate cancer. Abberivation: ADPC, androgen-dependent prostate cancer; CRPC, castrated prostate cancer; RNA1 AFAP1-Asl, Actin fiber-associated protein 1-anti-RNA1; miRNAs, MicroRNAs.

Wang K ，Sun H ，Sun T ，Qu H ，Xie Q ，Lv H ，Hu B ... -  《-》

Long non-coding RNA AFAP1-AS1 facilitates ovarian cancer progression by regulating the miR-107/PDK4 axis.

Liu B ，Yan L ，Chi Y ，Sun Y ，Yang X ... -  《Journal of Ovarian Research》

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.

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). 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. 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. 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.

Tang M ，Wu H ，Zhang H ，Xu X ，Jiang B ，Chen Q ，Wei Y ，Qian H ，Han L ... -  《-》