RNF111/Arkadia is regulated by DNA methylation and affects TGF-β/Smad signaling associated invasion in NSCLC cells

Chen, Hongbing; Yang, Tianjie; Li, Zhe; Wang, Longqiang; Yang, Haiping; Tong, Xin; Yang, Wentao; Zhao, Jun; Gu, Yunbin; Chen, Yongbing; Zhang, Hong Tao

doi:10.1016/j.lungcan.2015.07.010

Cited by 13 publications

(6 citation statements)

References 36 publications

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“…In fact, TGF‐β/SMAD signaling acts as a metastasis promoter by inducing EMT in late‐stage tumors (Akhurst & Derynck, 2001; Xu & Pasche, 2007; Chen et al, 2015). In this study, TGFβR1, an essential receptor of TGF‐β/SMAD signaling, was found highly expressed in metastatic LUAD tissues.…”

Section: Discussionmentioning

confidence: 99%

Quaking 5 suppresses TGF‐β‐induced EMT and cell invasion in lung adenocarcinoma

Wang

Tong

et al. 2021

EMBO Reports

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Quaking (QKI) proteins belong to the signal transduction and activation of RNA (STAR) family of RNA-binding proteins that have multiple functions in RNA biology. Here, we show that QKI-5 is dramatically decreased in metastatic lung adenocarcinoma (LUAD). QKI-5 overexpression inhibits TGF-b-induced epithelialmesenchymal transition (EMT) and invasion, whereas QKI-5 knockdown has the opposite effect. QKI-5 overexpression and silencing suppresses and promotes TGF-b-stimulated metastasis in vivo, respectively. QKI-5 inhibits TGF-b-induced EMT and invasion in a TGFbR1-dependent manner. KLF6 knockdown increases TGFbR1 expression and promotes TGF-b-induced EMT, which is partly abrogated by QKI-5 overexpression. Mechanistically, QKI-5 directly interacts with the TGFbR1 3 0 UTR and causes post-transcriptional degradation of TGFbR1 mRNA, thereby inhibiting TGF-b-induced SMAD3 phosphorylation and TGF-b/SMAD signaling. QKI-5 is positively regulated by KLF6 at the transcriptional level. In LUAD tissues, KLF6 is lowly expressed and positively correlated with QKI-5 expression, while TGFbR1 expression is up-regulated and inversely correlated with QKI-5 expression. We reveal a novel mechanism by which KLF6 transcriptionally regulates QKI-5 and suggest that targeting the KLF6/QKI-5/TGFbR1 axis is a promising targeting strategy for metastatic LUAD.

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Section: Discussionmentioning

confidence: 99%

Quaking 5 suppresses TGF‐β‐induced EMT and cell invasion in lung adenocarcinoma

Wang

Tong

et al. 2021

EMBO Reports

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“…Tumor cells can secrete specific receptors and chemokines to create a cell microenvironment facilitating their own proliferation, invasion into surrounding normal cells and distant metastasis (4,17). The role of RNF111 in lung cancer has been investigated by scholars, and it has been found that RNF111 promotes cancer growth and plays a key role in early cancer cell metastasis (29); however, its functions vary in different types of cancer (30). For example, RNF111 has been shown to exert an inhibitory effect on colon cancer metastasis (31).…”

Section: Discussionmentioning

confidence: 99%

circRNA RNF111 regulates the growth, migration and invasion of gastric cancer cells by binding to miR‑27b‑3p

et al. 2020

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hsa_circ_0001982 [circRNA ring finger protein 111 (RNF111)] has been found to promote cancer growth; however, its role in gastric cancer (GC) remains unclear. The present study examined the effects of circR-RNF111 on the growth, migration and invasion of GC cells and aimed to elucidate the underlying molecular mechanisms. The expression levels of circR-RNF111 and miR-27b-3p in GC tissues and GC cell lines were detected by reverse transcription-quantitative PCR (RT-qPCR). StarBase v2.0 and dual-luciferase assay were used to predict and analyze the association between circR-RNF111 and miR-27b-3p. The effects of circR-RNF111 and miR-27b-3p on cell growth, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8) assay, colony formation assay, flow cytometry, wound-healing assay and Transwell assay, respectively. In addition, western blot analysis was performed to determine the expression levels of genes related to cell apoptosis and epithelial-mesenchymal transition (EMT). The results revealed that circR-RNF111 and miR-27b-3p were closely related to the clinicopathological characteristics of GC, and that circR-RNF111 and miR-27b-3p negatively correlated and were abnormally expressed in GC. circR-RNF111 acted as a sponge of miR-27b-3p. The silencing of circR-RNF111 significantly inhibited GC cell viability, colony formation, migration and invasion, and exerted a pro-apoptotic effect. miR-27b-3p inhibitor promoted the proliferation, migration and invasion of GC cells, and inhibited cell apoptosis. In addition, circR-RNF111 silencing significantly decreased the expression levels of Bcl2, Vimentin and N-cadherin, and increased those of cleaved caspase-3 and E-cadherin. Furthermore, miR-27b-3p inhibition reversed the regulatory effects of circR-RNF111 silencing on the GC cells. On the whole, the findings of the present study demonstrate that circR-RNF111 is involved in the regulation of growth, migration and invasion of GC cells by binding to miR-27b-3p.

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“…RNF111, also known as Arkadia, is an E3 ligase characterized by multiple N-terminal nuclear localization signals, three tandem SIMs, and a C-terminal RING-finger domain ( Erker et al., 2013 ; Kotter, Mootz, & Heuer, 2023 ; Sun & Hunter, 2012 ). Originally identified as a key regulator in embryonic development, RNF111 was found to play a crucial role in activating and amplifying TGF-β family signaling by ubiquitinating and degrading negative regulators of the TGF-β pathway, including Smad7, SnoN, and c-Ski ( Chen et al., 2015 ; Cunnington, Nazari, & Dixon, 2009 ; Koinuma et al., 2003 ; Liu et al., 2006 ; Nagano et al., 2007 ; Tian et al., 2015 ; Wu et al., 2021 ; Xu et al., 2021 ).…”

Section: Rnf111 and Its Role In Genome Maintenancementioning

confidence: 99%

Preserving genome integrity: The vital role of SUMO-targeted ubiquitin ligases

Han,

Mu,

Huang

2023

Cell Insight

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RNF111/Arkadia is regulated by DNA methylation and affects TGF-β/Smad signaling associated invasion in NSCLC cells

Cited by 13 publications

References 36 publications

Quaking 5 suppresses TGF‐β‐induced EMT and cell invasion in lung adenocarcinoma

Quaking 5 suppresses TGF‐β‐induced EMT and cell invasion in lung adenocarcinoma

circRNA RNF111 regulates the growth, migration and invasion of gastric cancer cells by binding to miR‑27b‑3p

Preserving genome integrity: The vital role of SUMO-targeted ubiquitin ligases

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