LNCAROD promotes the proliferation and migration of gastric cancer: a bioinformatics analysis and experimental validation.

Gastric cancer (GC) is a heterogeneous disease at the molecular and clinical levels. The diffuse subtype is associated with more aggressive behavior and poor prognosis than the intestinal subtype. Epithelial-to-mesenchymal transition (EMT) may be involved in the diffuse mesenchymal phenotype. Long non-coding RNA (lncRNA) deregulation plays a vital role in GC development and progression. Here, we aimed to comprehensively disclose lncRNAs associated with GC diffuse/mesenchymal type. RNA-sequencing expression profiles of patients with stomach adenocarcinoma and the corresponding clinical data were downloaded from The Cancer Genome Atlas database. Differentially expressed lncRNAs related to tumor samples and diffuse subtype were identified. The lncRNA activating regulator of DKK1 (LNCAROD) was experimentally studied. Furthermore, a lncRNA-miRNA-mRNA network was constructed to identify potential biological functions of LNCAROD. LNCAROD expression was detected by reverse transcription-quantitative polymerase chain reaction in GC cell lines. LNCAROD expression was silenced using the small interference RNA strategy. Cell proliferation and migration were evaluated using colony formation assay, scratch wound healing, and Transwell migration assays. LNCAROD was significantly upregulated in some GC cells. The knocking down of LNCAROD significantly reduced cell proliferation and migration. LNCAROD-miR-181-PROX1 axis was introduced as a potential regulatory mechanism by which LNCAROD may exert its functions in cells. Our findings highlight that LNCAROD is involved in cell proliferation and migration in GC and supports its implicit role in regulating EMT. It may serve as a potential diagnostic and therapeutic target in GC. In addition, LNCAROD may function through the possible regulatory axis in GC development.

N6-methyladenosine-mediated upregulation of LNCAROD confers radioresistance in esophageal squamous cell carcinoma through stabilizing PARP1.

BACKGROUND: Radiotherapy is a primary therapeutic modality for esophageal squamous cell carcinoma (ESCC), but its effectiveness is still restricted due to the resistance of cancer cells to radiation. Long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) have been shown to play significant roles in tumour radioresistance. However, the precise manifestation and role of m6A-modified lncRNAs in ESCC radioresistance remain unclear. METHODS: Bioinformatics analysis was conducted to identify m6A-modified lncRNAs implicated in the radioresistance of ESCC. A series of functional experiments were performed to investigate the function of LNCAROD in ESCC. Methylated RNA immunoprecipitation, chromatin isolation by RNA purification-mass spectrometry, RNA immunoprecipitation, and co-immunoprecipitation experiments were performed to explore the mechanism of m6A-mediated upregulation of LNCAROD expression and the downstream mechanism enhancing the radioresistance of ESCC. The efficacy of LNCAROD in vivo was assessed using murine xenograft models. RESULTS: Herein, we identified LNCAROD as a novel METTL3-mediated lncRNA that enhanced radioresistance in ESCC cells and was post-transcriptionally stabilised by YTHDC1. Moreover, we confirmed that LNCAROD prevented ubiquitin-proteasome degradation of PARP1 protein by facilitating PARP1-NPM1 interaction, thereby contributing to homologous recombination-mediated DNA double-strand breaks repair and enhancing the radiation resistance of ESCC cells. Silencing LNCAROD in a nude mouse model of ESCC in vivo resulted in slower tumour growth and increased radiosensitivity. CONCLUSION: Our findings enhance the understanding of m6A-modified lncRNA-driven machinery in ESCC radioresistance and underscore the significance of LNCAROD in this context, thereby contributing to the development of a potential therapeutic target for ESCC patients.

Long Noncoding RNA AROD Inhibits Host Antiviral Innate Immunity via the miR-324-5p-CUEDC2 Axis.

Long noncoding RNAs (lncRNAs) are a class of noncoding RNAs that are involved in multiple biological processes. Here, we report a mechanism through which the lnc-AROD-miR-324-5p-CUEDC2 axis regulates the host innate immune response, using influenza A virus (IAV) as a model. We identified that host lnc-AROD without protein-coding capability is composed of 975 nucleotides. Moreover, lnc-AROD inhibited interferon-ß expression, as well as interferon-stimulated genes ISG15 and MxA. Furthermore, in vivo assays confirmed that lnc-AROD overexpression increased flu virus pathogenicity and mortality in mice. Mechanistically, lnc-AROD interacted with miR-324-5p, leading to decreased binding of miR-324-5p to CUEDC2. Collectively, our findings demonstrated that lnc-AROD is a critical regulator of the host antiviral response via the miR-324-5p-CUEDC2 axis, and lnc-AROD functions as competing endogenous RNA. Our results also provided evidence that lnc-AROD serves as an inhibitor of the antiviral immune response and may represent a potential drug target. IMPORTANCE lnc-AROD is a potential diagnostic and discriminative biomarker for different cancers. However, so far the mechanisms of lnc-AROD regulating virus replication are not well understood. In this study, we identified that lnc-AROD is downregulated during RNA virus infection. We demonstrated that lnc-AROD enhanced CUEDC2 expression, which in turn inhibited innate immunity and favored IAV replication. Our studies indicated that lnc-AROD functions as a competing endogenous RNA that binds miR-324-5p and reduces its inhibitory effect on CUEDC2. Taken together, our findings reveal that lnc-AROD plays an important role during the host antiviral immune response.