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Oral submucosal fibrosis (OSF) is one of the pre‐cancerous lesions of oral squamous cell carcinoma (OSCC). Its malignant rate is increasing, but the mechanism of malignancy is not clear. We previously have elucidated the long non‐coding RNA (lncRNA) expression profile during OSF progression at the genome‐wide level. However, the role of lncRNA ADAMTS9‐AS2 in OSF progression via extracellular communication remains unclear. lncRNA ADAMTS9‐AS2 is down‐regulated in OSCC tissues compared with OSF and normal mucous tissues. Low ADAMTS9‐AS2 expression is associated with poor overall survival. ADAMTS9‐AS2 is frequently methylated in OSCC tissues, but not in normal oral mucous and OSF tissues, suggesting tumour‐specific methylation. Functional studies reveal that exosomal ADAMTS9‐AS2 suppresses OSCC cell growth, migration and invasion in vitro. Mechanistically, exosomal ADAMTS9‐AS2 inhibits AKT signalling pathway and regulates epithelial‐mesenchymal transition markers. Through profiling miRNA expression profile regulated by exosomal ADAMTS9‐AS2, significantly enriched pathways include metabolic pathway, PI3K‐Akt signalling pathway and pathways in cancer, indicating that exosomal ADAMTS9‐AS2 exerts its functions through interacting with miRNAs during OSF progression. Thus, our findings highlight the crucial role of ADAMTS9‐AS2 in the cell microenvironment during OSF carcinogenesis, which is expected to become a marker for early diagnosis of OSCC.

Background: We investigated whether ADAMTS9-AS2 and CADM2 were related to esophageal squamous cell carcinoma (ESCC). Methodology: ESCC microarray datasets and reverse transcriptase qualitative PCR were used to analyze ADAMTS9-AS2 and CADM2 expression. Results: The GSE120356 and GSE33810 datasets identified ADAMTS9-AS2 and CADM2 as the candidates and ADAMTS9-AS2 and CADM2 expression was downregulated in ESCC. ADAMTS9-AS2 and CADM2 were positively correlated with ESCC. ADAMTS9-AS2 and CADM2 expression could discriminate ESCC from normal tissue. Five-year overall survival was shorter in underexpressed ADAMTS9-AS2 patients, and CADM2 expression level was related to 5-year overall survival. ADAMTS9-AS2 and CADM2 expression were independent prognosis indicators in ESCC patients. Conclusion: Our findings shed new light on the clinical significance of ADAMTS9-AS2 and CADM2 in ESCC carcinogenesis.

Nowadays, research on CSCs is still in an initial stage, and there are few studies reporting the successful isolation and identification of CSCs. In the present study, we attempted to isolate CSCs through cultivating the cell line MKN45 in defined serum‐free medium and study the expression of stem cell markers or related proteins (Oct3/4, Sox2, Nanog and CD44) in CSCs. Moreover, immunofluorescence staining was performed to validate the stem cell markers of spheroid body‐forming cells. Further experiments were used to evaluate the SPOP expression in tumorsphere cells. In addition, ADAMTS9‐AS2 is a lncRNA that contributes to the genesis and development of many cancers, including gastric cancer (GC). We found ADAMTS9‐AS2 functioned as an anti‐oncogene and positively correlated with the expression of SPOP in GC tissues by combining bioinformatics analyses. Furthermore, we reported that ADAMTS9‐AS2 regulated the expression of SPOP in GC cells and tumorsphere cells to inhibit GC progression. Together, our results demonstrated that SPOP and ADAMTS9‐AS2 can be potential targets for GC treatment.

Objective: The mechanism of long non-coding RNA ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) has been insufficiently explored in ovarian cancer (OC). Here, the action of ADAMTS9-AS2 in OC with the involvement of DNA methyhransferase l (DNMT1) and septin 6 (SEPT6) was explored. Methods: Epithelial OC tissue and ovarian epithelial tissue specimens were collected to test ADAMTS9-AS2, DNMT1 and SEPT6 expression. An appropriate cell line was screened out and transfected with highly expressed ADAMTS9-AS2 or SEPT6 or lowly expressed DNMT1 to detect their roles in biological functions of OC cells. Tumorigenesis of OC cells in nude mice was projected to validate cell experiment results. The interactions between ADAMTS9-AS2 with DNMT1/SEPT6 were tested. Results: Elevated DNMT1 and reduced ADAMTS9-AS2 and SEPT6 were detected in OC. ADAMTS9-AS2 bound to both DNMT1 and SEPT6. Restoring ADAMTS9-AS2 or SEPT6 or depleting DNMT1 diminished OC cell viability, invasion and migration, arrested cell cycle and accelerated apoptosis in vitro, and repressed tumor growth in vivo. Conclusion: Collectively, ADAMTS9-AS2 fights against OC through recruiting DNMT1 and up-regulating SEPT6.

Long non-coding RNAs (lncRNAs), as competitive endogenous RNAs (ceRNAs), play a critical role in biological processes of cancer. However, the roles of specific lncRNAs in ceRNA network of lung adenocarcinoma (LUAD) remains largely unclear. Herein, we identified the roles of lncRNA ADAMTS9-AS1/AS2 (ADAMTS-AS1/AS2) in lung adenocarcinoma by bioinformatics analyses and functional verification. First, differentially expressed genes ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were screened out from GSE130779. Then the expression correlation of these three genes was analyzed. The results showed that ADAMTS9-AS1, ADAMTS9-AS2 and ADAMTS9 were down-regulated in LUAD, and were positively correlated with each other. After that, miRcode was used to find miR-150 which binds to ADAMTS9-AS1/ADAMTS9-AS2/ADAMTS9. Next, co-expression analysis and functional enrichment analyses were performed to further analyze differentially expressed genes. The results showed that the differentially expressed genes were mainly enriched in Beta3 integrin cell surface interactions and epithelial-to-mesenchymal transition. Finally, the cell functions of ADAMTS9-AS1 and ADAMTS9-AS2 in A549 and NCI-H1299 cell lines were verified. In vitro cell studies confirmed that ADAMTS9-AS1 and ADAMTS9-AS2 play an inhibitory role in LUAD cells.

BackgroundLong non-coding RNAs (lncRNAs) are key regulators of triple-negative breast cancer (TNBC) progression, but further work is needed to fully understand the functional relevance of these non-coding RNAs in this cancer type. Herein, we explored the functional role of the lncRNA ADAMTS9-AS2 in TNBC.MethodsNext-generation sequencing was conducted to compare the expression of different lncRNAs in TNBC tumor and paracancerous tissues, after which ADAMTS9-AS2differential expression in these tumor tissues was evaluated via qPCR. The functional role of this lncRNA was assessed by overexpressing it in vitro and in vivo. FISH and PCR were used to assess the localization of ADAMTS9-AS2within cells. Downstream targets of ADAMTS9-AS2 signaling were identified via RNA pulldown assays and transcriptomic sequencing.ResultsThe expression ofADAMTS9-AS2 was decreased in TNBC tumor samples (P < 0.05), with such downregulation being correlated with TNM stage, age, and tumor size. Overexpressing ADAMTS9-AS2 promoted the apoptotic death and cell cycle arrest of tumor cells in vitro and inhibited tumor growth in vivo. From a mechanistic perspective, ADAMTS9-AS2 was found to control the expression of RPL22 and to thereby modulate TGF-β signaling to control TNBC progression.ConclusionADAMTS9-AS2 controls the expression of RPL22 and thereby regulates TNBC malignancy via the TGF-β signaling pathway.

Long noncoding RNAs (lncRNAs) are a type of noncoding RNA transcript that are characterized by lack of protein-coding capacity. The vital role of lncRNAs in tongue squamous cell carcinoma (TSCC) is attracting increasing attention. In the present study, we identify a key lncRNA regulating TSCC metastasis and investigated the underlying mechanism. Our results indicate that the lncRNA ADAMTS9-AS2 is most significantly upregulated in TSCC tissues from patients with lymph node metastasis and is closely associated with poor prognosis. Furthermore, ADAMTS9-AS2 knockdown in TSCC cells leads to a inhibition of cell migration and invasion and reverses TGF-β1 induced EMT. ADAMTS9-AS2 knockdown also inhibits TSCC cell growth in vitro and in vivo. In addition, we show that ADAMTS9-AS2 is a cytoplasmic lncRNA that shares the miRNA response elements (MREs) of miR-600 with EZH2, which is confirmed by a luciferase reporter assay and AGO2-dependent RNA immunoprecipitation (RIP). In summary, our results demonstrate an explicit oncogenic role of ADAMTS9-AS2 in TSCC tumorigenesis via competition with miR-600, suggesting a new regulatory mechanism of ADAMTS9-AS2 and providing a potential therapeutic target for TSCC patients.