Comprehensive analysis of the lncRNA‑associated competing endogenous RNA network in breast cancer

Wang, Jing‑Jing; Huang, Yongzhen; Song, Wei; Li, Yi‐Fan; Wang, Han; Wang, Wenjie; Huang, Min

doi:10.3892/or.2019.7374

Cited by 31 publications

(34 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In recent years, The dysregulation and/or prognostic roles of KPNA2 were reported in many tumors including esophageal squamous cell carcinoma (Song et al, 2019), breast cancer (Groheux et al, 2018;Wang et al, 2019a), myeloma (Kriegsmann et al, 2019;Tachita et al, 2020), clear cell renal cell carcinoma (Müller et al, 2019), oral cancer (Wang et al, 2018), bladder cancer (Jeong et al, 2017), and colorectal cancer (Ostasiewicz et al, 2016;Jeong et al, 2017). The immune-related roles of KPNA2 were also shown in tumors.…”

Section: Introductionmentioning

confidence: 99%

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Zhang

Gao

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

Karyopherin α2 (KPNA2) was reported to be overexpressed and have unfavorable prognostic effects in many malignancies including hepatocellular carcinoma (HCC). Although its contributions to inflammatory response were reported in many studies, its specific associations with immune infiltrations and immune pathways during cancer progression were unclear. Here, we aimed to identify new markers for HCC diagnosis and prognosis through KPNA2-associated immune analyses. RNA-seq expression data of HCC datasets were downloaded from The Cancer Genome Atlas and International Cancer Genome Consortium. The gene expressions were counts per million normalized. The infiltrations of 24 kinds of immune cells in the samples were evaluated with ImmuCellAI (Immune Cell Abundance Identifier). The Spearman correlations of the immune infiltrations with KPNA2 expression were investigated, and the specific positive correlation of B-cell infiltration with KPNA2 expression in HCC tumors was identified. Fifteen genes in KEGG (Kyoto Encyclopedia of Genes and Genomes) B-cell receptor signaling pathway presented significant correlations with KPNA2 expression in HCC. Among them, GRB2 and NRAS were indicated to be independent unfavorable prognostic factors for HCC overall survival. Clinical Proteomic Tumor Analysis Consortium HCC dataset was investigated to validate the results at protein level. The upregulation and unfavorable prognostic effects of KPNA2 and GRB2 were confirmed, whereas, unlike its mRNA form, NRAS protein was presented to be downregulated and have favorable prognostic effects. Through receiver operating characteristic curve analysis, the diagnostic potential of the three proteins was shown. The RNA-binding proteins (RBPs) of KPNA2, NRAS, and GRB2, downloaded via The Encyclopedia of RNA Interactomes, were investigated for their clinical significance in HCC at protein level. An eight-RBP signature with independent prognostic value and dysregulations in HCC was identified. All the RBPs were significantly correlated with MKI67 expression and at least one of KPNA2, GRB2, and NRAS at protein level in HCC, indicating Zhang et al. KPNA2-Associated Immune Analyses in HCC Frontiers in Genetics | www.frontiersin.org 2 October 2020 | Volume 11 | Article 593273 their roles in HCC progression and the regulation of the three proteins. We concluded that KPNA2, GRB2, NRAS, and their RBPs might have coordinating roles in HCC immunoregulation and progression. They might be new markers for HCC diagnosis and prognosis predication and new targets for HCC immunotherapy.

show abstract

Section: Introductionmentioning

confidence: 99%

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Zhang

Gao

et al. 2020

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…In recent years, studies have increasingly demonstrated that lncRNAs function as ceRNAs that may sponge miRNAs to decrease their expression and activity, which would thereby regulate the suppressive effects on miRNA targets ( 43 - 45 ). In the present study, lncLocator analysis revealed that LINC01232 was mostly localized in the cytoplasm, consistent with the results of the cell cytosolic/nuclear fraction isolation experiment.…”

Section: Discussionmentioning

confidence: 99%

Long intergenic non‑coding RNA LINC01232 contributes to esophageal squamous cell carcinoma progression by sequestering microRNA‑654‑3p and consequently promoting hepatoma‑derived growth factor expression

et al. 2020

View full text Add to dashboard Cite

Long intergenic non-coding RNA 01232 (LINC01232) was identified as a critical regulator of the development of pancreatic adenocarcinoma. The present study investigated the expression and regulatory roles of LINC01232 in esophageal squamous cell carcinoma (ESCC). The main aim of the present study was to elucidate the underlying mechanisms through which LINC01232 affects the malignancy of ESCC. Initially, LINC01232 expression in ESCC was analyzed using the TCGA and GTEx databases and was confirmed using reverse transcription-quantitative polymerase chain reaction. ESCC cell proliferation, apoptosis and migration and invasion were assessed using the Cell Counting kit-8 assay, flow cytometric analysis, and migration and invasion assays, respectively. ESCC tumor growth in vivo was examined using a xenograft mouse model. As shown by the results, a high LINC01232 expression was detected in ESCC tissues and cell lines. LINC01232 downregulation suppressed the proliferation, migration and invasion of ESCC cells, and promoted cell apoptosis in vitro . In addition, LINC01232 depletion restricted tumor growth in vivo . Mechanistically, LINC01232 was shown to function as an microRNA-654-3p (miR-654-3p) sponge in ESCC cells, and hepatoma-derived growth factor (HDGF) was identified as a direct target of miR-654-3p. LINC01232 could bind competitively to miR-654-3p and decrease its expression in ESCC cells, thereby promoting HDGF expression. Rescue experiments reconfirmed that the effects of LINC01232 deficiency in ESCC cells were restored by increasing the output of the miR-654-3p/HDGF axis. On the whole, the present study demonstrates that LINC01232 plays a tumor-promoting role during the progression of ESCC by regulating the miR-654-3p/HDGF axis. The LINC01232/miR-654-3p/HDGF pathway may thus provide a novel theoretical basis for the management of ESCC.

show abstract

“…KPNA2 has been first descripted in matched ductal carcinoma in situ (DCIS) and invasive lesions of the breast [28]. Furthermore, KPNA2 may be the primary determinant for transcription factors transporting and transcriptional activity in various cancers including breast cancer, melanoma, liver cancer, and lung cancer, and therefore is probably related to the cancer cell growth and invasion [15,[29][30][31]. These findings suggest that high KPNA2 expression in patients with breast may be related with worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Analyses of DNA methylation involved in the activation of nuclear karyopherin alpha 2 leading to the progression and prognostic significance across human breast cancer

Cui

Liang

Hao

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Karyopherin alpha 2 (KPNA2) is a nuclear import factor that plays a crucial role in nucleocytoplasmic transport, as well as cell proliferation, migration and invasion in several cancers. However, the roles of KPNA2 in breast cancer as well as the underlying molecular mechanisms have not been elucidated. Methods: To evaluate gene expression alterations during breast carcinogenesis, KPNA2 expression was analyzed using the Gene Expression Profiling Interactive Analysis and Oncomine analyses. The correlation between methylation and expression was analyzed using the MEXPRESS tool, UALCAN cancer database, and cBioPortal browser. Then, the expression and prognostic value of KPNA2 was investigated by our own breast cancer samples using RT-PCR. KPNA2 methylation level was detected by methylation-specific PCR. Results: We obtained the following important results. (1) KPNA2 expression was significantly higher in breast cancer than normal samples and regulated by aberrant DNA hypomethylation of promoter region. (2) Among patients with breast cancer, those with higher KPNA2 expression had a lower survival rate. (3) The major mutation type of KPNA2 in breast cancer samples was missense mutation. (4) Homer1 was able to promote breast cancer progression may be through up-regulating TPX2 expression. Conclusions: Our findings suggest that aberrant DNA hypomethylation of promoter regions contributes to the aberrant expression of KPNA2 in breast cancer, which might be a potential indicator of poor prognosis.

show abstract

Comprehensive analysis of the lncRNA‑associated competing endogenous RNA network in breast cancer

Cited by 31 publications

References 80 publications

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

KPNA2-Associated Immune Analyses Highlight the Dysregulation and Prognostic Effects of GRB2, NRAS, and Their RNA-Binding Proteins in Hepatocellular Carcinoma

Long intergenic non‑coding RNA LINC01232 contributes to esophageal squamous cell carcinoma progression by sequestering microRNA‑654‑3p and consequently promoting hepatoma‑derived growth factor expression

Analyses of DNA methylation involved in the activation of nuclear karyopherin alpha 2 leading to the progression and prognostic significance across human breast cancer

Contact Info

Product

Resources

About