Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer

Huang, Min-Yu; Long, Yi; Jin, Yuzhu; Ya, Wentong; Meng, Dongdong; Qin, Tianzi; Su, Lize; Zhou, Wei; Wu, Jichao; Huang, Chunhe; Huang, Qun

doi:10.21037/tau-21-81

Cited by 16 publications

(20 citation statements)

References 42 publications

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“…Utilizing the TCGA database, this study detected higher SERPINE2 mRNA expression in UBUC, which has been associated with poor survival. The abovementioned finding is consistent with those of a study by Huang et al [31]. Recently, Lin et al [32] also identified that SERPINE2 could predict OS in patients with UBUC based on five cohorts.…”

Section: Discussionsupporting

confidence: 90%

SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

et al. 2021

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Recent studies have reported that SERPINE2 contributes to the development of various cancers. However, its association with urothelial carcinoma (UC) remains unclear. In this study, data on urinary bladder UC (UBUC) cases from The Cancer Genome Atlas (TCGA) database were used to investigate the prognostic value of SERPINE2 mRNA expression. Then, SERPINE2 expression was analyzed with tissue microarrays constructed from 117 upper tract UC (UTUC) and 84 UBUC tissue specimens using immunohistochemical staining. Results were compared to clinicopathologic data by multivariate analysis. In the TCGA database, high SERPINE2 mRNA expression indicated a poor prognosis in patients with UBUC. Furthermore, Mann–Whitney U test showed that high SERPINE2 immunoexpression was significantly associated with adverse pathologic parameters including invasion, high grade, coexistence of UC in situ, and advanced pT stage (all p < 0.05, except for a marginal association with high-grade UBUC, p = 0.066). Kaplan–Meier analysis revealed that high SERPINE2 expression was associated with worse overall survival (OS; UTUC, p = 0.003; UBUC, p = 0.014) and disease-free survival (UTUC, p = 0.031; UBUC, p = 0.033). Moreover, multivariate analysis identified high SERPINE2 expression as an independent prognostic factor for OS (UTUC, p = 0.002; UBUC, p = 0.024). Taken together, our findings demonstrated that increased SERPINE2 expression is associated with adverse pathologic features and may serve as a prognostic biomarker for UC.

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Section: Discussionsupporting

confidence: 90%

SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

et al. 2021

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“…Yang et al (32) indicated that SPTBN2 was a potential driver gene in breast cancer and endometrial cancer. Huang et al (33) identified the significant upregulation of SPTBN2 expression in bladder cancer tumor samples compared with normal samples, and SPTBN2 expression was associated with a poor prognosis in bladder cancer. Zhang et al (34) discovered that the expression of SPTBN2 was significantly upregulated in colorectal cancer patients with distant metastasis.…”

Section: Discussionmentioning

confidence: 99%

SPTBN2, a New Biomarker of Lung Adenocarcinoma

Dong

Huang

et al. 2021

Front. Oncol.

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ObjectivesThe roles played by β-III-spectrin, also known as spectrin beta, non-erythrocytic 2 (SPTBN2), in the occurrence and development of lung adenocarcinoma (LUAD) have not been previously examined. Our study aimed to reveal the relationship between the SPTBN2 expression and LUAD.Materials and MethodsTwenty pairs of LUAD tissues and adjacent tissues were collected from patients diagnosed and treated at the Thoracic Surgery Department of The First Affiliated Hospital of Zhengzhou University from July 2019 to September 2020. RNA sequencing (RNA-seq) analysis determined that the expression of SPTBN2 was higher in LUAD samples than in adjacent normal tissues. The expression levels of SPTBN2 were examined in various databases, including the Cancer Cell Line Encyclopedia (CCLE), Gene Expression Omnibus (GEO), and Human Protein Atlas (HPA). The Search Tool for the Retrieval of Interacting Genes (STRING) online website was used to examine protein–protein interactions involving SPTBN2, and the results were visualized by Cytoscape software. The Molecular Complex Detection (MCODE) plug-in for Cytoscape software was used to identify functional modules of the obtained protein–protein interaction (PPI) network. Gene enrichment analysis was performed, and survival analysis was conducted using the Kaplan–Meier plotter. The online prediction website TargetScan was used to predict SPTBN2-targeted miRNA sequences by searching for SPTBN2 sequences. Finally, we verified the expression of SPTBN2 in the obtained tissue samples using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The human lung cancer cell lines A549 and H1299 were selected for the transfection of small interfering RNA (siRNA) targeting SPTBN2 (si-SPTBN2), and the knockdown efficiency was evaluated by RT-qPCR. The cellular proliferation, migration, and invasion capacities of A549 and H1299 cells were determined using the cell counting kit-8 (CCK-8) proliferation assay; the wound-healing assay and the Transwell migration assay; and the Matrigel invasion assay, respectively.ResultsThe expression of SPTBN2 in non–small cell lung cancer (NSCLC) ranked 13th among cancer cell lines based on the CCLE database. At the mRNA and protein levels, the expression levels of SPTBN2 were higher in LUAD tissues than in normal lung tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that proteins related to SPTBN2 were enriched in apoptotic and phagosomal pathways. Kaplan–Meier survival analysis revealed that SPTBN2 expression was significantly related to the prognosis of patients with LUAD. The TargetScan database verified that miR-16 was a negative regulator of SPTBN2 mRNA expression. The results of the CCK-8 cell proliferation assay revealed that SPTBN2 knockdown significantly inhibited the cell proliferation abilities of A549 and H1299 cells. The wound-healing assay indicated that SPTBN2 knockdown resulted in reduced migration after 48 h compared with the control group. The Transwell migration and invasion test revealed that the migration and invasion abilities were greatly decreased by SPTBN2 knockdown compared with control conditions.ConclusionWe uncovered a novel gene, SPTBN2, that was significantly upregulated in LUAD tissues relative to normal tissue expression. SPTBN2 is highly expressed in LUAD, positively correlated with poor prognosis, and can promote the proliferation, migration, and invasion of LUAD cells.

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“…The role of the lncRNA/miRNA/mRNA network in various biological progression has been elucidated in recent decades. As a major cause of cancer initiation and progression, multiple gene mutations have drawn wide scientific interests, and considerable effort has been exerted to elucidate the molecular mechanisms that contribute to tumorigenesis via the lncRNA/miRNA/mRNA network, such as bladder cancer, hepatocellular carcinoma, osteosarcoma, gastric cancer, oral cancer, and CC [ 21 – 26 ]. lncRNA-CTS regulates CC progression via the miR-505/ZEB2 axis [ 27 ], lncRNA TP73-AS1 modulates CC development via the miR-329-3p/ARF1 axis [ 28 ], lncRNA CAR10 promotes CC progression via the miR-125b-5p/PDPK1 pathway [ 29 ], and lncRNA DANCR aggravates CC development via the miR-335-5p/ROCK1 axis [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNA SNHG15 Induced by SOX12 Promotes the Tumorigenic Properties and Chemoresistance in Cervical Cancer via the miR-4735-3p/HIF1a Pathway

Jiang

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Cervical cancer (CC) is one of the most common malignancies in females, with high prevalence and mortality globally. Despite advances in diagnosis and therapeutic strategies developed in recent years, CC is still a major health burden worldwide. The molecular mechanisms underlying the development of CC need to be understood. In this study, we aimed to demonstrate the role of lncRNA SNHG15 in CC progression. Using qRT-PCR, we determined that lncRNA SNHG15 is highly expressed in CC tumor tissues and cells. lncRNA SNHG15 knockdown also reduces the tumorigenic properties of CC in vitro, as determined using the MTT, EdU, flow cytometry, and transwell assays. Using bioinformatics analysis, RNA pull-down, ChIP, and luciferase reporter assays, we verified the molecular mechanisms of lncRNA SNHG15 in CC progression and found that lncRNA SNHG15 expression in CC cells is transcriptionally regulated by SOX12; moreover, lncRNA SNHG15 promotes CC progression via the miR-4735-3p/HIF1a axis. This study can provide a potential target for CC diagnosis or therapeutic strategies in the future.

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Comprehensive analysis of the lncRNA-miRNA-mRNA regulatory network for bladder cancer

Cited by 16 publications

References 42 publications

SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

SERPINE2 Overexpression Is Associated with Poor Prognosis of Urothelial Carcinoma

SPTBN2, a New Biomarker of Lung Adenocarcinoma

lncRNA SNHG15 Induced by SOX12 Promotes the Tumorigenic Properties and Chemoresistance in Cervical Cancer via the miR-4735-3p/HIF1a Pathway

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