Dysregulated genes targeted by microRNAs and metabolic pathways in bladder cancer revealed by bioinformatics methods

Zhang, Lu; Feng, Cuihua; Zhou, Yamin; Zhou, Qiong

doi:10.3892/ol.2018.8602

Cited by 10 publications

(12 citation statements)

References 47 publications

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“…CALM1 is composed of Ca 2+ -binding EF-hands, and participates in signaling pathways that modulates proliferation, motility and differentiation [ 14 ]. Several studies found that the expression level of CALM1 was markedly associates with many kinds of cancer, including bladder cancer [ 15 ], prostate cancer [ 16 ] and nasopharyngeal carcinoma [ 17 ]. As far as CALM is concerned, numerous investigations have been carried out on mechanistic aspects, mainly in the cell proliferation, programmed cell death and autophagy.…”

Section: Introductionmentioning

confidence: 99%

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

et al. 2021

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Background Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. Method Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9(Clustered regularly interspaced short palindromic repeats)was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib. Results Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group. Conclusion Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.

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Section: Introductionmentioning

confidence: 99%

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

et al. 2021

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“…In the current study, many miRNAs have been found to be abnormally expressed in BC, playing a role in promoting or inhibiting tumors 30–33. Abnormal expression in miRNA tumor tissues is reflected in two aspects: up-regulation and down-regulation.…”

Section: Discussionmentioning

confidence: 68%

<p>The functions of microRNA-124 on bladder cancer</p>

Cao¹,

Xu²,

Zhao³

et al. 2019

OTT

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Background: To detect the expression of miR-124 in bladder cancer (BC) cell lines and tissue specimens and to analyze its association with the growth of the BC cells. Methods: Quantitative real-time polymerase chain reaction (qPCR) was applied to examine the expression of miR-124 in BC cell lines and tissues. The function of miR-124 in modulating cell proliferation was assessed in BC cells with miRNA-124 overexpression; the cell viability was identified by Cell Count Kit-8; flow cytometry was employed to detect the cell cycle; the expressions of E2F3, cyclin-dependent kinase 4 (CDK4), Ki-67 and vascular endothelial growth factor (VEGF) were tested by qPCR and Western blot; angiogenesis experiment was performed to analysis changes in angiogenesis rate; and bioinformatics prediction and dual luciferase reporter system were employed to identify the target of miR-124. Results: Survival curve data showed that the expression of MicroRNA-124 was positively correlated with survival. MicroRNA-124 expression was significantly decreased in BC cell lines and tissues. Bioinformatics prediction and dual luciferase reporter system verified CDK4 as a direct target of miR-124, which regulated the proliferation of BC cells by directly inhibiting CDK4. BC cells over-expressing miR-124 showed significantly inhibited cell viability, decreased angiogenesis rate, prevented cell proliferation and diminished the expression of E2F3, CDK4, Ki-67 and VEGF. All of these changes were reversed by over-expressing CDK4. Conclusion: MicroRNA-124 suppressed the proliferation of CRC cells by directly targeting CDK4, which provides a target for improving the therapeutic effect of BC.

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“…CALM1 is composed of Ca 2+ -binding EF-hands, and participates in signaling pathways that modulates proliferation, motility and differentiation [14]. Several studies found that the expression level of CALM1 was markedly associates with many kinds of cancer, including bladder cancer [15], prostate cancer [16] and nasopharyngeal carcinoma [17]. As far as CALM is concerned, numerous investigations have been carried out on mechanistic aspects, mainly in the cell proliferation, programmed cell death and autophagy.…”

Section: Introductionmentioning

confidence: 99%

“…In this study we focus on CALM1. CALM is composed of Ca 2+ -binding EF-hands, and participates in signaling pathways that modulates proliferation, motility and differentiation [15]. Several studies found that the expression level of CALM1 was markedly associates with many kinds of cancer, including bladder cancer [16], prostate cancer [17] and nasopharyngeal carcinoma [18].…”

Section: Introductionmentioning

confidence: 99%

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

Liu¹,

Han²,

Liu³

et al. 2021

Preprint

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Background: Calmodulin1 (CALM1) has been identified as one of the overexpression genes in a variety of cancers and EGFR inhibitor have been widely used in clinical treatment but it is unknown whether CALM1 and epidermal growth factor receptor (EGFR) have a synergistic effect in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to explore the synergistic effects of knock-out CALM1 combined with EGFR inhibitor (Afatinib) and to elucidate the role of CALM1 in sensitizing the resistance to Afatinib in ESCC. Method: Immunohistochemistry (IHC) and qRT-PCR were used to examine the expression of CALM1 and EGFR in ESCC tissues. Kaplan–Meier survival analysis was used to analyze the clinical and prognostic significance of CALM1 and EGFR expression in ESCC. Furthermore, to evaluate the biological function of CALM1 in ESCC, the latest gene editing technique CRISPR/Cas9（Clustered regularly interspaced short palindromic repeats）was applied to knockout CALM1 in ESCC cell lines KYSE150, Eca109 and TE-1. MTT, flow cytometry, Transwell migration, scratch wound-healing and colony formation assays were performed to assay the combined effect of knock-out CALM1 and EGFR inhibitor on ESCC cell proliferation and migration. In addition, nude mice xenograft model was used to observe the synergistic inhibition of knock-out CALM1 and Afatinib.Results: Both CALM1 and EGFR were found to be significantly over-expressed in ESCC compared with paired normal control. Over-expressed CALM1 and EGFR were significantly associated with clinical stage, T classification and poor overall prognosis, respectively. In vitro, the combined effect of knock-out CALM1 mediated by the lentivirus and EGFR inhibitor was shown to be capable of inhibiting the proliferation, inducing cell cycle arrest at G1/S stage and increasing apoptosis of KYSE-150 and Eca109 cells; invasion and migration were also suppressed. In vivo, the results of tumor weight and total fluorescence were markedly reduced compared with the sgCtrl-infected group and sgCAML1 group.Conclusion: Our data demonstrated that knock-out of CALM1 could sensitize ESCC cells to EGFR inhibitor, and it may exert oncogenic role via promotion of EMT. Taken together, CALM1 may be a tempting target to overcome Afatinib resistance.

show abstract

Dysregulated genes targeted by microRNAs and metabolic pathways in bladder cancer revealed by bioinformatics methods

Cited by 10 publications

References 47 publications

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

<p>The functions of microRNA-124 on bladder cancer</p>

CALM1 promotes progression and dampens chemosensitivity to EGFR inhibitor in esophageal squamous cell carcinoma

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