Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression

Chen, Yongsheng; Xu, Yongpeng; Liu, Wenhua; Li, Dechao; Wang, Huan; Li, Chang-Fu

doi:10.3389/fonc.2021.649778

Cited by 9 publications

(6 citation statements)

References 31 publications

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“…Transwell assay demonstrated that sh-KCNMB2-AS1 repressed both the migration and invasion of ESCA cells compared with sh-NC ( Figure 1(g,h) ). Since tumor cell stemness is believed to be the cause tumor recurrence and metastasis, the prevention of tumor cell stemness can hinder the development of the tumor to a certain degree [ 41 ]. Then, we investigated the influence of KCNMB2-AS1 on cell stemness in ESCA.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, KCNMB2-AS1 knockdown inhibited ESCA cell growth and motion, and KCNMB2-AS1 overexpression promoted ESCA cell growth and motion, suggesting an oncogenic role of KCNMB2-AS1 in ESCA. In addition, tumor cell stemness is believed to be the cause tumor recurrence and metastasis, and the prevention of tumor cell stemness can hinder the development of the tumor to a certain degree [ 41 ]. Several lncRNAs such as FMR1 antisense RNA 1 (FMR1-AS1) [ 47 ], small nucleolar RNA host gene 12 (SNHG12) [ 48 ], HLA complex P5 (HCP5) [ 49 ], fer-1 like family member 4 (pseudogene) (FER1L4) [ 50 ] were reported to regulate ESCA cell stemness.…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis

Liu

et al. 2021

Bioengineered

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Esophageal cancer (ESCA), as a common cancer worldwide, is a main cause of cancer-related mortality. Comprehensive studies on molecular mechanism of ESCA have been carried out. Though numerous long noncoding RNAs (lncRNAs) was reported to participate in the occurrence and development of ESCA, the potential role of lncRNA potassium calcium-activated channel subfamily M regulatory beta subunit 2 (KCNMB2) antisense RNA 1 (KCNMB2-AS1) in ESCA remains to be discovered. This study intends to investigate the detailed function and molecular mechanism of KCNMB2-AS1 in ESCA. Gene expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell invasion and migration were measured by wound healing assay and Transwell assay. Luciferase reporter assay was adopted to validate the interaction between KCNMB2-AS1 and miR-3194-3p. Western blotting was performed to assess protein levels. We discovered that KCNMB2-AS1 was significantly upregulated in ESCA. KCNMB2-AS1 downregulation suppressed the growth, invasion, migration and stemness of ESCA cells. KCNMB2-AS1 bound with miR-3194-3p, and glycogen phosphorylase L (PYGL) was a direct target of miR-3194-3p. KCNMB2-AS1 upregulated PYGL expression by directly binding with miR-3194-3p. Additionally, PYGL overexpression abolished the inhibitory influence of KCNMB2-AS1 depletion on ESCA cell behaviors. Collectively, lncRNA KCNMB2-AS1 promotes ESCA development through targeting the miR-3194-3p/ PYGL axis, which might provide theoretical basis to explore novel biomarkers for ESCA treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis

Liu

et al. 2021

Bioengineered

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“…SMAD5 is closely related to the occurrence and progression of various cancers. Chen et al [ 40 ] reported that SMAD5 was highly expressed in bladder cancer. We found that SMAD5 was highly expressed in HCC, suggesting that SMAD5 might play a positive role in the progression of HCC.…”

Section: Discussionmentioning

confidence: 99%

Role of lncRNA LINC01194 in hepatocellular carcinoma via the miR-655-3p/SMAD family member 5 axis

Liu

Jun-kai

et al. 2022

Bioengineered

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Long non-coding RNAs (lncRNAs) are involved in developing hepatocellular carcinoma (HCC). The present study explored the role of lncRNA LINC01194, which is upregulated in HCC tissues and might be a vital regulator in HCC progression. Levels of LINC01194, microRNA (miR)-655-3p, and SMAD family member 5 (SMAD5) were assessed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The bioactivity of Huh-7 cells was assessed using cell counting kit-8 and transwell assays and flow cytometry. Western blotting was conducted to measure the expression of invasion- and apoptosis-related proteins. The relationships between lncRNA LINC01194 and miR-655-3p, and miR-655-3p and SMAD5 were predicted using StarBase and TargetScan, and further verified using a dual-luciferase reporter assay. LINC01194 was overexpressed in HCC cells and in clinical samples. ILINC01194 silencing suppressed proliferation and migration; however, it promoted apoptosis in HCC cell lines. We also confirmed that miR-655-3p could bind to LINC01194, and miR-655-3p was downregulated in HCC. The upregulation of miR-655-3p suppressed HCC cell invasion and migration, and enhanced the number of apoptotic cells. SMAD5, which was overexpressed in HCC cell lines, was directly targeted by miR-655-3p. Therefore, LINC01194 promoted HCC development by decreasing miR-655-3p expression and may serve as a promising therapeutic target for HCC patients.

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“…In cancer biology, miRNAs are implicated in a variety of malignancies by modulating different downstream targets [ 40–43 ]. In BC cells, miRNAs are involved in the regulation of cell proliferation, migration, and invasion, self-renewal, angiogenesis, as well as the development of resistance [ 44–48 ]. In our results, we further revealed that circLONP2 could bind to miR-584-5p and inhibit its function.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA LONP2 regulates proliferation, invasion, and apoptosis of bladder cancer cells by sponging microRNA-584-5p

et al. 2022

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Bladder cancer (BC) is the most frequent type of urinary tumor and a barely treatable disease. Although extensive efforts have been invested in the research of BC, the underlying etiology and pathophysiology remain unclear. CircLONP2 is a circular RNA implicated in the development of many cancers, and miR-584-5p and YAP1 have been reported to contribute to the progression of BC. In this research, we presented novel evidence supporting circLONP2/miR-584-5p/YAP1 axis as a novel regulatory module in the progression of BC. We analyzed the expression of circLONP2 between precancerous BC samples and normal tissues using a published RNA-seq dataset. The expression of circLONP2 was also validated in clinical samples and cell lines by quantitative RT-PCR. Small interfering RNA (siRNA) and miRNA inhibitor was utilized to modulate the expression of circLONP2 and miR-584-5p and investigate their functions on cell proliferation and invasion. Luciferase reporter assay and RNA pull-down were performed to confirm the functional interactions among circLONP2/miR-584-5p/YAP1. CircLONP2 was significantly upregulated in precancerous BC tissues and BC cells. CircLONP2 depletion inhibited cell viability, proliferation, and invasion of BC cell lines, which could be partially rescued by miR-584-5p inhibitor. Further experiments indicated that miR-584-5p regulates cell viability, proliferation, and invasion via directly targeting YAP1. In summary, our work indicates that circLONP2 plays an oncogenic function in BC by regulating miR-584-5p/YAP1 axis, and its interaction with miR-584-5p provides a potential strategy to target BC.

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Long Noncoding RNA KCNMB2-AS1 Promotes SMAD5 by Targeting miR-3194-3p to Induce Bladder Cancer Progression

Cited by 9 publications

References 31 publications

Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis

Long noncoding RNA KCNMB2-AS1 promotes the development of esophageal cancer by modulating the miR-3194-3p/PYGL axis

Role of lncRNA LINC01194 in hepatocellular carcinoma via the miR-655-3p/SMAD family member 5 axis

Circular RNA LONP2 regulates proliferation, invasion, and apoptosis of bladder cancer cells by sponging microRNA-584-5p

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