CircKEAP1 Suppresses the Progression of Lung Adenocarcinoma via the miR-141-3p/KEAP1/NRF2 Axis

Wang, Yanbo; Ren, Fenghai; Sun, Dawei; Liu, Jing; Liu, Benkun; He, Yunlong; Pang, Sainan; Shi, Bowen; Zhou, Fucheng; Yao, Lei; Lang, Yaoguo; Xu, Shidong; Wang, Junfeng

doi:10.3389/fonc.2021.672586

Cited by 15 publications

(14 citation statements)

References 34 publications

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“…In dong’s study of breast cancer in vivo and in vitro, low expression of MEG3 sponge miR-141-3p affected cell proliferation performance and apoptosis, which was negatively correlated with high expression of miR-141-3p [ 31 ]. Meanwhile, circKEAP1 inhibited the progression of LUAD by targeting miR-141-3p and opened a new idea for the treatment of LUAD [ 32 ], which was consistent with our study. The previous analysis confirmed that ATP2B1-AS1 specifically binds to miR-141-3p to participate in the development of LUAD and play a regulatory role in the prognosis of patients from the aspects of cell function and biological mechanism.…”

Section: Discussionsupporting

confidence: 90%

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression

Chen,

Huang,

Jin

2024

J Cardiothorac Surg

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Background LncRNA ATP2B1-AS1 (ATP2B1-AS1) is involved in the occurrence and development of various diseases, while the relationship between lung adenocarcinoma (LUAD) and ATP2B1-AS1 is unclear. This study was to investigate the expression of ATP2B1-AS1 in LUAD and its influence on survival and prognosis of patients. Methods LUAD tissue samples from patients participating in this study were collected, and the expression levels of ATP2B1-AS1 and miR-141-3p in LUAD sampleswere detected by real-time quantitative polymerase chain reaction (RT-qPCR). The effect of ATP2B1-AS1 on the growth of A549 cells was investigated through cell counting kit-8 (CCK-8) and transwell experiments. Besides, the prognostic value of ATP2B1-AS1 in LUAD was assessed via Kaplan-Meier curve and multivariate Cox regression. Results ATP2B1-AS1 was downregulated in LUAD tissues and cells, whereas miR-141-3p was upregulated. After pcDNA3.1-ATP2B1-AS1 was transfected into A549 cells, the proliferation ability of A549 cells was decreased, and the migration level and invasion of A549 cells were also inhibited. High expression of ATP2B1-AS1 sponge miR-141-3p exerted prognostic value. Conclusions ATP2B1-AS1 sponge miR-141-3p alleviated the progression of LUAD, and ATP2B1-AS1 may be deemed as a prognostic marker for LUAD.

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Section: Discussionsupporting

confidence: 90%

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression

Chen,

Huang,

Jin

2024

J Cardiothorac Surg

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“…18 Interestingly, circKEAP1 has been suggested to competitively bind to microRNA (miRNA)−141-3p and relived miR-141-3p suppression for its host gene (Keap-1), thus suppressing the LUAD progression via the Nrf2/Keap-1 pathway. 19 Our mechanistical investigations revealed that circPIBF1 silencing could prevent the nuclear translocation of Nrf2. While additional rescue experiments using the pathway activator exhibited that induction of the Nrf2/Keap-1 pathway could mitigate the pro-pyroptotic effects of circPIBF1 Intriguingly, histone writer EP300 has been revealed to bind to circSOD2 promoter and trigger its promoter H3K27ac modification, which further stimulated circSOD2 expression in hepatocellular carcinoma.…”

Section: Overexpression Of Ep300 or Sod2 Impairs The Repressing Effec...mentioning

confidence: 82%

“…Noncoding RNA‐mediated regulation of NRF2 and interplay between Nrf2 and noncoding RNAs have added new layers of complexity to already intricate nature of Nrf2, while there are little clues about interplay between circRNAs and Nrf2 in cancers 18 . Interestingly, circKEAP1 has been suggested to competitively bind to microRNA (miRNA)−141‐3p and relived miR‐141‐3p suppression for its host gene (Keap‐1), thus suppressing the LUAD progression via the Nrf2/Keap‐1 pathway 19 . Our mechanistical investigations revealed that circPIBF1 silencing could prevent the nuclear translocation of Nrf2.…”

Section: Discussionmentioning

confidence: 99%

Transcription factor Nrf2 binds to circRNAPIBF1 to regulate SOD2 in lung adenocarcinoma progression

Zhang

Chen

Huang

et al. 2022

Molecular Carcinogenesis

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Emerging evidence indicates that circular RNAs (circRNAs) play important roles in disease development, especially in cancers. Analysis of circRNA expression microarrays from the Gene Expression Omnibus database revealed that circPIBF1 was highly upregulated in lung adenocarcinoma (LUAD). The main aim of this study was to probe the function of circPIBF1 in pyroptosis of LUAD cells and the signal transduction pathways involved. CircPIBF1 was significantly overexpressed in LUAD and was related to the dismal prognosis of patients with LUAD. CircPIBF1 could bind to nuclear factor erythroid 2‐related factor 2 (Nrf2), which further promoted the expression of superoxide dismutase 2 (SOD2). In addition, Nrf2 was also observed to recruit histone acetyltransferase E1A binding protein p300 (EP300) to enhance H3K27ac modification of SOD2, thus modulating the Nrf2‐Keap1 signaling pathway. Moreover, we found that knockdown of circPIBF1 significantly suppressed the expression of SOD2 in cells and LUAD cell growth, while enhanced the expression of pyroptosis‐related factors, which were further reversed by overexpression of SOD2 or EP300. Collectively, our findings suggest a direct involvement of circPIBF1 in pyroptosis‐related LUAD carcinogenesis and implicate a role of Nrf2/EP300/SOD2 signaling in this process.

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“…The aim of the present study was to identify a potential therapeutic target for patients with LUAD, a type of lung cancer that accounts for ~60% of all cases and has a 5-year survival rate of <20% ( 2 , 7 ). Although significant progress has been made in the molecular targeted therapy of LUAD, particularly for those with specific mutations in EGFR, ALK, RET and ROS1 ( 3 , 24 – 27 ), the high heterogeneity and complex molecular patterns of LUAD limit the applicability of these targeted therapies, thus leaving a number of patients without effective treatment options ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

“…Lung cancer is a leading cause of cancer-associated mortality worldwide, and is frequently associated with a poor prognosis due to being diagnosed at an advanced stage ( 1 ). The most prevalent histological subtype of lung cancer is lung adenocarcinoma (LUAD), which accounts for ~60% of cases globally ( 2 ). In recent years, notable progress has been made in LUAD treatment with the use of molecular targeted therapies ( 3 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation

et al. 2023

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Significant advancements have been achieved in the area of molecular targeted therapy for lung adenocarcinoma (LUAD). However, the complex molecular patterns and high heterogeneity of LUAD confine the efficacy of these therapies to a specific subset of patients; therefore, it is necessary to explore novel targets for LUAD treatment. The expression levels of anillin (ANLN) in LUAD were analyzed using the Gene Expression Profiling Interactive Analysis database. Furthermore, the association between ANLN gene expression and patient survival outcomes was evaluated using the Kaplan-Meier Plotter. Subsequently, small interfering RNA (siRNA) transfection was performed to knock down ANLN in A549 and H1299 cell lines, after which, TUNEL, colony formation and Transwell assays were conducted to assess cell death, colony formation and migration, respectively. Additionally, western blot analysis was performed to analyze the expression levels of caspase-1, interleukin (IL)-18 (IL-18), IL-1β, NLR family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD domain (ASC) and cleaved gasdermin D (GSDMD) following ANLN knockdown. The results revealed that ANLN mRNA expression was significantly increased in LUAD tissues compared with adjacent normal samples. Furthermore, the expression levels of ANLN displayed an increasing trend with advancing clinical stage. Furthermore, patients with high ANLN expression levels exhibited poor overall survival rates compared with those with low ANLN expression levels. Subsequent ANLN knockdown experiments indicated elevated cell death rate, and reduced colony formation and migration in both A549 and H1299 cells. Additionally, ANLN knockdown resulted in increased protein expression levels of pyroptosis-associated molecules, including caspase-1, NLRP3, cleaved-GSDMD, IL-1β, ASC and IL-18 in both A549 and H1299 cells. In conclusion, ANLN represents an important gene and a promising therapeutic target for LUAD. Its potential as a therapeutic target makes it an interesting candidate for further exploration in the development of novel treatment strategies for LUAD.

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CircKEAP1 Suppresses the Progression of Lung Adenocarcinoma via the miR-141-3p/KEAP1/NRF2 Axis

Cited by 15 publications

References 34 publications

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression

Regulation of overexpression lncRNA ATP2B1-AS1 on lung adenocarcinoma progression

Transcription factor Nrf2 binds to circRNAPIBF1 to regulate SOD2 in lung adenocarcinoma progression

Knockdown of ANLN inhibits the progression of lung adenocarcinoma via pyroptosis activation

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