Tumor suppressive long non-coding RNA AFDN-DT inhibits gastric cancer invasion via transcriptional regulation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE139326 | GEO | 2020/04/17
REPOSITORIES: GEO
Similar Datasets
Project description:Emerging evidence has revealed that dysregulation of lncRNA is associated with the initiation and progression of cancer. However, the function of these lncRNAs in cancer remains largely unexplored. Here, we reported that AFDN-DT, an lncRNA that is repressed in gastric cancers (GC), functions as a tumour suppressor by inhibiting cell growth and metastasis through transcriptional repression of genes involved in metastasis. Using in vitro and in vivo models, we demonstrated that overexpression of AFDN-DT inhibited the proliferation and metastasis of GC. We found that AFDN-DT was located at the nucleus and interacted with the chromatin in gastric cells. Further, ChIRP-seq experiments and RNA-seq analysis revealed that AFDN-DT directly bound to the promoter regions and regulated the expression of genes essential for malignant transformation. Moreover, we demonstrated that DNA hypermethylation could repress AFDN-DT expression and treatment with DNA methylation inhibitors restored its expression. Collectively, the results of our study demonstrated the tumour suppressive role of AFDN-DT in GC and elucidated the transcription regulatory role of tumour suppressive lncRNAs, which can serve as potential prognostic markers for GC.
| S-EPMC7077530 | biostudies-literature
Project description:Tumor suppressive long non-coding RNA AFDN-DT inhibits gastric cancer invasion via transcriptional regulation
| PRJNA579322 | ENA
Project description:Edwardsiella tarda DT genome sequencing
| PRJNA66369 | ENA
Project description:Gastric cancer (GC) remains a leading cause of cancer‑associated mortality globally. Emerging evidence suggests that microRNAs (miRs) function as oncogenes or tumor suppressors, contributing to various aspects of cancer progression, including invasion and metastasis. In the present study, the specific role of miR‑299‑3p in the invasion of GC cells was investigated. The expression level of miR‑299‑3p was measured using reverse transcription‑quantitative PCR and in situ hybridization in human GC tissues. Effects of miR‑299‑3p on GC cell invasion were determined by Transwell assay. Bioinformatics and luciferase reporter assays were performed to identify and verify the downstream effectors of miR‑299‑3p. miR‑299‑3p expression analysis in clinical GC samples revealed a significant downregulation of miR‑299‑3p compared with non‑tumor tissues. Inhibition of miR‑299‑3p promoted the invasive abilities of GC cells, whereas its overexpression significantly suppressed cell invasion. Bioinformatics and luciferase reporter assays identified heparanase (HPSE) as a direct target of miR‑299‑3p, the ectopic expression of which reversed the impairment in cell invasion induced by miR‑299‑3p upregulation. Furthermore, HPSE expression was negatively associated with miR‑299‑3p levels in human GC tissues. Overall, the present study indicated that miR‑299‑3p functions as a tumor suppressor by directly targeting HPSE, highlighting its potential as a target for the treatment of GC.
| S-EPMC6691259 | biostudies-literature
Project description:Acinetobacter baumannii strain:DT-544 | isolate:DT-544 Genome sequencing and assembly
| PRJNA600819 | ENA
Project description:Mycobacterium avium subsp. paratuberculosis DT 3 Genome Sequencing
| PRJNA72217 | ENA
Project description:Mycobacterium avium subsp. avium DT 78 Genome Sequencing
| PRJNA72221 | ENA
Project description:Gastric cancer is one of the most common cancers in the world, and long non-coding RNAs (lncRNAs) play a crucial role in proliferation, metastasis, and invasion of gastric cancer. However, there are very few researches focusing on the effects of lncRNAs on metastatic gastric cancer. In this research, we identify one kind of lncRNA, called AK025387, which is highly expressed in metastatic gastric cancer samples compared with non-metastatic gastric cancer samples. The expression of AK025387 is significantly positively correlated with lymph node metastasis. The in situ hybridization demonstrates that AK025387 is located in both nucleus and cytoplasm, but mostly in cytoplasm. AK025387 promotes gastric cancer cells migratory and invasive ability, but it inhibits apoptosis in vitro. Furthermore, AK025387 regulates Raf-1, mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK), and extracellular signal-regulated kinase (ERK) and is involved in mitogen-activated protein kinase (MAPK) signaling pathway to perform its biological functions. We conclude that AK025387 is highly expressed in metastatic gastric cancer, and its biological functions suggest the potential of AK025387 to be a biomarker of metastatic gastric cancer.
| S-EPMC7251172 | biostudies-literature
Project description:HGC27 gastric cancer cells were manipulated to express mutant p53
2019-06-07 | GSE132333 | GEO
Project description:Long non-coding RNA (lncRNA) ADAM metallopeptidase with thrombospondin type 1 motif 9 antisense RNA 2 (ADAMTS9-AS2) is involved in various types of cancer, such as ovarian cancer, lung cancer and clear cell renal cell carcinoma. However, the roles of ADAMTS9-AS2 in liver cancer are not completely understood. The present study aimed to determine the functional role of ADAMTS9-AS2 in human liver cancer and investigate the potential underlying molecular mechanisms. The expression levels of ADAMTS9-AS2 and ADAMTS9 were determined following ADAMTS9-AS2 overexpression and knockdown. The results indicated that ADAMTS9-AS2 overexpression and knockdown increased and decreased ADAMTS9 mRNA and protein expression levels, respectively, indicating that alterations in ADAMTS9 expression corresponded with ADAMTS9-AS2 expression. Subsequently, the effects of ADAMTS9-AS2 on liver cancer cell proliferation, migration and invasion were analyzed by performing Cell Counting Kit-8, wound healing and Transwell assays, respectively. The results demonstrated that ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion. Finally, the effect of ADAMTS9 on PI3K/AKT/mTOR signaling pathway-associated proteins [AKT, phosphorylated-AKT, phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit β (PIK3CB), mTOR and phosphorylated-mTOR], several key autophagy-related proteins [light chain 3-I/II (LC3-I/II), beclin 1 (BECN1) and sequestosome 1 (SQSTM1)] and apoptosis-related proteins (Bax and Bcl-2) was detected via western blotting. The results suggested that ADAMTS9-AS2 downregulated the phosphorylation of AKT and mTOR, the protein expression level of PIK3CB, as well as the expression levels of autophagy protein SQSTM1 and antiapoptotic protein Bcl-2. By contrast, ADAMTS9-AS2 upregulated the expression levels of autophagy proteins LC3-II and BECN1, and the proapoptotic protein Bax. Collectively, ADAMTS9-AS2 inhibited liver cancer cell proliferation, migration and invasion via inhibiting the PI3K/AKT/mTOR signaling pathway. The present study provided a novel insight into the role of ADAMTS9-AS2 in liver cancer.
| S-EPMC8027749 | biostudies-literature