Long Noncoding RNA AFAP1-AS1 Promoted Tumor Growth and Invasion in Cholangiocarcinoma.

Long non-coding RNAs (lncRNAs) have been shown to play important roles in a wide range of pathophysiological processes, including cancer progression. Our previous study has shown that AFAP1-AS1 was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the expression and biological functions of lncRNA AFAP1-AS1 in intrahepatic cholangiocarcinoma (CCA) remains largely unknown. The expression level of AFAP1-AS1 was measured in 56 pairs of human cholangiocarcinoma tumor tissues and corresponding adjacent normal bile duct tissues. The correlation between AFAP1-AS1 and the clinicopathological features were evaluated by chi-square test. The effects of AFAP1-AS1 on CCA cells were determined by CCK-8 assay, clone formation assay, flow cytometry and transwell assay. Finally, to determine the effect of AFAP1-AS1 on tumor growth in vivo, AFAP1-AS1 knockdowned CCLP-1 cells were subcutaneously into nude mice to evaluate tumor growth. In this study, we found that lncRNA AFAP1-AS1 was increased in CCA tissues and patients with high AFAP1-AS1 expression had a shorter overall survival. SiRNA-mediated AFAP1-AS1 knockdown significantly decreased cell proliferation of the CCA cells, with downregulation of C-myc and Cycling D1 in vitro. Furthermore, AFAP1-AS1 silencing inhibited cell migration partly due to decrease the expression of MMP-2 and MMP-9. In addition, CCLP-1 cells with AFAP1-AS1 knockdown were injected into nude mice to investigate the effect of AFAP1-AS1 on the tumorigenesis in vivo. Taken together, our findings suggested that AFAP1-AS1 might promote the CCA progression and provided a novel potential therapeutic target for CCA.

Lu X ，Zhou C ，Li R ，Deng Y ，Zhao L ，Zhai W ... -  《-》

Upregulation of the long non-coding RNA AFAP1-AS1 affects the proliferation, invasion and survival of tongue squamous cell carcinoma via the Wnt/β-catenin signaling pathway.

Wang ZY ，Hu M ，Dai MH ，Xiong J ，Zhang S ，Wu HJ ，Zhang SS ，Gong ZJ ... -  《Molecular Cancer》

Overexpression of Long Non-Coding RNA NNT-AS1 Correlates with Tumor Progression and Poor Prognosis in Osteosarcoma.

Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play critical regulatory roles in cancers, including osteosarcoma. A previous study showed that Nicotinamide Nucleotide Transhydrogenase-antisense RNA1 (NNT-AS1) was aberrantly expressed in several types of cancer. However, the potential biological roles and regulatory mechanisms of NNT-AS1 in osteosarcoma progression remain unknown. Quantitative RT-PCR was performed to examine the expression of NNT-AS1 in human tissues and cells. The biological functions of NNT-AS1 were determined by CCK-8, colony formation, Flow cytometry and Transwell assays in vitro. A mouse xenograft model was performed to investigate the effect of NNT-AS1 on tumor growth in vivo. In this study, we found the expression of NNT-AS1 was significantly increased in tumor tissues compared to adjacent normal tissues. Furthermore, upregulated NNT-AS1 expression predicted poor prognosis and was an independent and significant risk factor for osteosarcoma patient survival. Further experiments revealed that NNT-AS1 knockdown significantly inhibited cell proliferation by inducing cell cycle arrest and promoting apoptosis in osteosarcoma cells. Moreover, NNT-AS1 silencing suppressed cell migration and invasion in vitro. In a tumor xenograft model, knockdown of NNT-AS1 suppressed tumor growth of OS-732 cells in vivo. Taken together, these findings indicate that NNT-AS1 functions as an oncogene in osteosarcoma and could be a novel diagnostic and therapeutic target for osteosarcoma.

Ye H ，Lin J ，Yao X ，Li Y ，Lin X ，Lu H ... -  《-》

Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo.

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.

Yao Y ，Sun Y ，Jiang Y ，Qu L ，Xu Y ... -  《-》

lncRNA AFAP1-AS1 Promotes Migration and Invasion of Non-Small Cell Lung Cancer via Up-Regulating IRF7 and the RIG-I-Like Receptor Signaling Pathway.

Accumulating evidence has highlighted the importance of long non-coding RNAs (lncRNAs) as competing endogenous RNAs (ceRNAs) in tumor biology. Among others, actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) has been associated with non-small cell lung cancer (NSCLC). However, it remains unclear how AFAP1-AS1 participates in the development and progression of NSCLC. The peripheral blood samples were collected from patients with NSCLC. White blood cell subsets were classified and levels of interleukin (IL)-10, IL-12 and IFN-γ in serum were measured. We then identified its target gene of AFAP1-AS1 via bioinformatics methods. NSCLC cell line with the highest expression of AFAP1-AS1, i.e. H1975 was selected for in vitro experiments. A series of inhibitor, vector and siRNA were employed to validate the regulatory mechanisms of AFAP1-AS1 in the development and progression of NSCLC. Cell proliferation was detected by MTT assay and EdU staining. Cell migration and invasion, and cell cycle and apoptosis were measured by transwell assay and flow cytometry, respectively. A high expression of AFAP1-AS1 was identified in NSCLC, alongside with a reduced level of IL-12 and increased levels of IL-10 and interferon (IFN)-γ. Aberrant expressions of AFAP1-AS1 were associated with pathological grade, TNM staging and metastatic potential of NSCLC. AFAP1-AS1 could activate interferon regulatory factor (IRF)7, the retinoid-inducible protein (RIG)-I-like receptor signaling pathway and Bcl-2 in vitro. Over-expression of AFAP1-AS1 promoted NSCLC cell proliferation, invasion and migration while inhibiting cell apoptosis. lncRNA AFAP1-AS1 promotes migration and invasion of non-small cell lung cancer via up-regulating IRF7 and the RIG-I-like receptor signaling pathway.

Tang XD ，Zhang DD ，Jia L ，Ji W ，Zhao YS ... -  《-》