hsa_circ_0062389 promotes the progression of non-small cell lung cancer by sponging miR-103a-3p to mediate CCNE1 expression

Technol Cancer Res Treat

et al. 2020

Objective: Although microRNA-103a (miR-103a) dysfunction has been implicated in various cancers, its relevance to non-small cell lung cancer (NSCLC) has not been clarified. This study was conducted to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC. Methods: Kaplan–Meier analysis was carried out to assess the relationship between overall survival of NSCLC patients and miR-103a expression. Reverse-transcription quantitative polymerase chain reaction and western blot analyses were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry, and Transwell assays were performed to characterize stemness. Dual luciferase reporter gene assays were used to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1). Finally, western blot analysis was used to assess the involvement of the Hippo pathway in NSCLC. Results: In NSCLC tissues and cells, miR-103a was expressed at low levels, whereas OTUB1 was expressed at high levels. Higher miR-103 expression levels were associated with a better prognosis for patients with NSCLC. When miR-103a was overexpressed, cell viability and stemness decreased, whereas apoptosis and cell cycle arrest were facilitated. The expression of phosphorylated YAP also decreased significantly. Opposite trends were observed after miR-103a silencing. OTUB1 expression and YAP phosphorylation decreased in the presence of miR-103a, and OTUB1 overexpression blocked the inhibitory effects of miR-103a on NSCLC cells. Conclusion: The miR-103a/OTUB1/Hippo axis may play a role in modulating the malignant behavior and stemness of cancer stem cells and thus could be a potential therapeutic target for the management of NSCLC.

Section: Introductionmentioning

confidence: 99%

MicroRNA-103a Curtails the Stemness of Non-Small Cell Lung Cancer Cells by Binding OTUB1 via the Hippo Signaling Pathway

Technol Cancer Res Treat

et al. 2020

“…Interestingly, several miRNAs, including miR-124a and miR-181b have been reported to inhibit stemness of CSCs and to overcome drug resistance in NSCLC [7,8]. In addition, miR-103a-3p expression was remarkably reduced in NSCLC tissues and cell lines, which was tightly correlated with dismal survival of NSCLC sufferers [9]. Moreover, miR-103a-3p was engaged in the tumor-suppressor role of linc00152 depletion in glioma stem cells [10].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-103a curtails the stemness of non-small cell lung cancer cells by binding to OTUB1 through the Hippo signaling pathway

et al. 2020

Preprint

Background Although dysfunction of microRNA-103a (miR-103a) has been implicated in various cancers, its relevance in non-small cell lung cancer (NSCLC) is unsettled. This study was designed with an aim to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC.Methods Kaplan-Meier analysis was carried out to study the correlation between overall survival of NSCLC patients and miR-103a expression. RT-qPCR and Western blot were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry as well as Transwell assays were conducted for characterizing the stemness. Dual-luciferase reporter gene assays were applied to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1).Results miR-103a expression was diminished in NSCLC tissues and cells, whereas OTUB1 expression was increased. Higher miR-103 expression indicated better prognosis for patients with NSCLC. After overexpression of miR-103a, the cell viability and stemness were diminished, while the cycle arrest and apoptosis rate were facilitated, and the expression of p-YAP decreased significantly. The opposite trends were observed after miR-103a silencing. miR-103a lowered the expression of OTUB1, while overexpression of OTUB1 blocked the inhibition effects of miR-103a on NSCLC.Conclusion miR-103a/OTUB1/Hippo axis plays a possible role in modulating the malignant behavior and stemness of cells which might function as a possible therapeutic option for the management of NSCLC.

“…Interestingly, several miRNAs, including miR-124a and miR-181b have been reported to inhibit stemness of CSCs and to overcome drug resistance in NSCLC [8,9]. In addition, miR-103a-3p expression was remarkably reduced in NSCLC tissues and cell lines, which was tightly correlated with dismal survival of NSCLC sufferers [10]. Moreover, miR-103a-3p was engaged in the tumor-suppressor role of linc00152 depletion in glioma stem cells [11].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-103a curtails the stemness of non-small cell lung cancer cells by binding to OTUB1 through the Hippo signaling pathway

et al. 2020

Preprint

Background: Although dysfunction of microRNA-103a (miR-103a) has been implicated in various cancers, its relevance in non-small cell lung cancer (NSCLC) is unsettled. This study was designed with an aim to examine the molecular mechanism underlying the regulatory role of miR-103a in NSCLC. Methods: Kaplan-Meier analysis was carried out to study the correlation between overall survival of NSCLC patients and miR-103a expression. RT-qPCR and Western blot were applied to evaluate the expression of relevant genes in tissues and cells. Sphere formation, MTS, flow cytometry as well as Transwell assays were conducted for characterizing the stemness. Dual-luciferase reporter gene assays were applied to clarify the binding relationship between miR-103a and ovarian tumor domain-containing ubiquitin aldehyde binding protein 1 (OTUB1). Results: miR-103a expression was diminished in NSCLC tissues and cells, whereas OTUB1 expression was increased. Higher miR-103 expression indicated better prognosis for patients with NSCLC. After overexpression of miR-103a, the cell viability and stemness were diminished, while the cycle arrest and apoptosis rate were facilitated, and the expression of p-YAP decreased significantly. The opposite trends were observed after miR-103a silencing. miR-103a lowered the expression of OTUB1, while overexpression of OTUB1 blocked the inhibition effects of miR-103a on NSCLC. Conclusion: miR-103a/OTUB1/Hippo axis plays a possible role in modulating the malignant behavior and stemness of cells which might function as a possible therapeutic option for the management of NSCLC.