STAT3-Induced lncRNA SNHG17 Exerts Oncogenic Effects on Ovarian Cancer through Regulating CDK6

Pan, Xuefeng; Guo, Zhiheng; Chen, Yanyan; Zheng, Shaojiang; Peng, Min; Yang, Yi; Wang, Zhenpeng

doi:10.1016/j.omtn.2020.08.006

Cited by 32 publications

(30 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to their ability to interact with different structures and molecules, lncRNAs have high heterogeneity and functional diversity [ 25 – 27 ]. As demonstrated previously, lncRNAs function importantly in regulating the cell fate determination, disease occurrence, and tumor progression [ 28 – 31 ]. Thus, this study focused on exploring the regulatory role of NORAD (also known as LINC00657) [ 32 ] in the stemness of PCSCs.…”

Section: Discussionmentioning

confidence: 83%

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

Yang

Liu

et al. 2021

J Transl Med

View full text Add to dashboard Cite

Background Cancer stem cells (CSCs) are key regulators in the processes of tumor initiation, progression, and recurrence. The mechanism that maintains their stemness remains enigmatic, although the role of several long noncoding RNAs (lncRNAs) has been highlighted in the pancreatic cancer stem cells (PCSCs). In this study, we first established that PCSCs overexpressing lncRNA NORAD, and then investigated the effects of NORAD on the maintenance of PCSC stemness. Methods Expression of lncRNA NORAD, miR-202-5p and ANP32E in PC tissues and cell lines was quantified after RNA isolation. Dual-luciferase reporter assay, RNA pull-down and RIP assays were performed to verify the interactions among NORAD, miR-202-5p and ANP32E. We then carried out gain- and loss-of function of miR-202-5p, ANP32E and NORAD in PANC-1 cell line, followed by measurement of the aldehyde dehydrogenase activity, cell viability, apoptosis, cell cycle distribution, colony formation, self-renewal ability and tumorigenicity of PC cells. Results LncRNA NORAD and ANP32E were upregulated in PC tissues and cells, whereas the miR-202-5p level was down-regulated. LncRNA NORAD competitively bound to miR-202-5p, and promoted the expression of the miR-202-5p target gene ANP32E thereby promoting PC cell viability, proliferation, and self-renewal ability in vitro, as well as facilitating tumorigenesis of PCSCs in vivo. Conclusion Overall, lncRNA NORAD upregulates ANP32E expression by competitively binding to miR-202-5, which accelerates the proliferation and self-renewal of PCSCs.

show abstract

Section: Discussionmentioning

confidence: 83%

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

Yang

Liu

et al. 2021

J Transl Med

View full text Add to dashboard Cite

show abstract

“…Among the overlapping three target genes, STAT3 is the most widely studied. STAT3, that is signal transducer and activator of transcription factor 3, relates not only to the proliferation, invasion, metastasis, apoptosis of ovarian cancer cells, but also chemotherapy resistance (Zhong et al 2021;Liu et al 2021;Pan et al 2020). BUB1 (budding uninhibited by benzimidazole 1) is a mitotic checkpoint protein that is overexpressed in various types of cancer, including breast cancer, gastric cancer, pancreatic cancer and so on (Han et al 2015;Piao et al 2019;Bai et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes, miRNAs and miRNAs-mRNA Regulatory Pathways for Chemotherapy Resistance in Ovarian Cancer

Wang

2021

Preprint

View full text Add to dashboard Cite

Background: Chemotherapy resistance, especially platinum resistance, is the main cause of poor prognosis of ovarian cancer. It is of great urgency to find molecular markers and mechanism related to platinum resistance in ovarian cancer.Methods: One mRNA dataset (GSE28739) and one miRNA dataset (GSE25202) were acquired from Gene Expression Omnibus (GEO) database. The GEO2R tool was used to screen out differentially expressed genes (DEGs) and differentially expressed miRNAs (DE-miRNAs) between platinum-resistant and platinum-sensitive ovarian cancer patients. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed using the DAVID to present the most visibly enriched pathways. Protein–protein interaction (PPI) of these DEGs was constructed based on the information of the STRING database. Hub genes related to platinum resistance were visualized by Cytoscape software. Then, we chose seven interested hub genes to further validate using qRT-PCR in A2780 ovarian cancer cell lines. And, at last, the TF-miRNA-target genes regulatory network was predicted and constructed using miRNet software.Results: A total of 63 upregulated DEGs, 124 downregulated DEGs, 4 upregulated miRNAs and 6 downregulated miRNAs were identified. From the PPI network, the top 10 hub genes were identified, which were associated with platinum resistance. Our further qRT-PCR showed that seven hub genes (BUB1, KIF2C, NUP43, NDC80, NUF2, CCNB2 and CENPN) were differentially expressed in platinum-resistant ovarian cancer cells. Furthermore, the upstream transcription factors (TF) for upregulated DE-miRNAs were SMAD4, NFKB1, SMAD3, TP53 and HNF4A. Three overlapping downstream target genes (KIF2C, STAT3 and BUB1) were identified by miRNet, which was regulated by hsa-miR-494.Conclusions: The TF-miRNA–mRNA regulatory pairs, that is TF (SMAD4, NFKB1 and SMAD3)-miR-494-target genes (KIF2C, STAT3 and BUB1), were established. In conclusion, the present study is of great significance to find the key genes of platinum resistance in ovarian cancer. Further study is needed to identify the mechanism of these genes in ovarian cancer.

show abstract

“…Our study subsequently indicated that STAT3 was the transcription factor for LINC00504. STAT3 serves as the transcription factor for lncRNA SNHG17 [22]. Moreover, STAT3 also plays an important role in TNBC.…”

Section: Discussionmentioning

confidence: 99%

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

Wu¹,

Jia²,

Zhang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Currently, long non-coding RNAs (lncRNAs) have been validated to exert critical influence on the malignant progression of triple-negative breast cancer (TNBC). LncRNA long intergenic non-protein coding RNA 504 (LINC00504) has been recently reported as a tumor facilitator in the cellular processes of several cancers. However, its function in TNBC remains unknown.Methods: CCK-8 and colony formation assays were used to detect the cell viability and proliferation in TNBC. Flow cytometry analysis was utilized to measure the cycle and apoptosis of TNBC cells. The levels of key proteins associated with cell apoptosis or the β-catenin pathway were detected through western blot analysis. The activity of the Wnt/β-catenin signaling pathway was measured by the TOP/FOP flash assay. ChIP assay was conducted to confirm the binding between LINC00504 and its transcription factor signal transducer and activator of transcription 3 (STAT3). RIP and luciferase reporter assays were used to detect and verify the interaction among LINC00504 and its downstream molecule.Results: LncRNA LINC00504 was upregulated in TNBC, and silenced LINC00504 suppressed cell proliferation and triggers cell cycle arrest at G0/G1 stage and cell apoptosis in TNBC cells. STAT3 can transcriptionally activate LINC00504 and LINC00504 served as a molecular sponge of microRNA (miR-4379). Kallikrein related peptidase 4 (KLK4) was the target gene of miR-4379 and activates the Wnt/β-catenin pathway. LINC00504 upregulated KLK4 via competitively binding with miR-4379 to activate the Wnt/β-catenin pathway in TNBC. The suppression on TNBC cell proliferation and the promotion on TNBC cell cycle arrest and apoptosis under LINC00504 knockdown were rescued by miR-4379 depletion or KLK4 overexpression.Conclusions: The LINC00504/miR-4379/KLK4 axis promotes cell growth and cell cycle progression as well as suppresses cell apoptosis through activating the Wnt/β-catenin pathway.

show abstract

STAT3-Induced lncRNA SNHG17 Exerts Oncogenic Effects on Ovarian Cancer through Regulating CDK6

Cited by 32 publications

References 38 publications

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

Long non-coding RNA NORAD promotes pancreatic cancer stem cell proliferation and self-renewal by blocking microRNA-202-5p-mediated ANP32E inhibition

Identification of Key Genes, miRNAs and miRNAs-mRNA Regulatory Pathways for Chemotherapy Resistance in Ovarian Cancer

The LINC00504/Mir-4739/KLK4 Axis Facilitates Cell Proliferation and Suppresses Cell Apoptosis Through Triggering The Wnt/Β-Catenin Pathway In Triple-Negative Breast Cancer Cells

Contact Info

Product

Resources

About