KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/ MAPK pathway in an m6A-dependent manner

Lin, Xi; Ye, Rongyi; Li, Zhiming; Du, Junbao; Huang, Yuji; Zhang, Bingli; Wang, Bo; Meng, Hao; Xian, Hongyi; Yang, Xingfen; Zhang, Xin; Zhong, Yizhou; Huang, Zhenlie

doi:10.1016/j.drup.2022.100908

Cited by 44 publications

(21 citation statements)

References 48 publications

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“…In addition, gefitinib resistance also occurs during the treatment of lung cancer. Knockdown of virus‐like m6A methyltransferase‐associated protein (KIAA1429) can inhibit the expression of MAP3K2 by recognising m6A methylation and inhibit gefitinib resistance 112 . Immunotherapy also promotes tumour tolerance as regulatory T cells express the CTLA‐4 immune checkpoint receptor, in which m6A‐modified circQSOX1 promotes PGAM1 expression, which in turn facilitates immune escape from CRC through activation of glycolysis and an anti‐CTLA‐4 therapeutic response, thereby promoting CRC tumourigenesis 113 …”

Section: The Emerging Roles Of Rna Methylation As Critical Regulators...mentioning

confidence: 99%

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

Chen,

Liu,

Zhang

et al. 2024

Clinical & Translational Med

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RNA methylation is widespread in nature. Abnormal expression of proteins associated with RNA methylation is strongly associated with a number of human diseases including cancer. Increasing evidence suggests that targeting RNA methylation holds promise for cancer treatment. This review specifically describes several common RNA modifications, such as the relatively well‐studied N6‐methyladenosine, as well as 5‐methylcytosine and pseudouridine (Ψ). The regulatory factors involved in these modifications and their roles in RNA are also comprehensively discussed. We summarise the diverse regulatory functions of these modifications across different types of RNAs. Furthermore, we elucidate the structural characteristics of these modifications along with the development of specific inhibitors targeting them. Additionally, recent advancements in small molecule inhibitors targeting RNA modifications are presented to underscore their immense potential and clinical significance in enhancing therapeutic efficacy against cancer.Key Points In this paper, several important types of RNA modifications and their related regulatory factors are systematically summarised. Several regulatory factors related to RNA modification types were associated with cancer progression, and their relationships with cancer cell migration, invasion, drug resistance and immune environment were summarised. In this paper, the inhibitors targeting different regulators that have been proposed in recent studies are summarised in detail, which is of great significance for the development of RNA modification regulators and cancer treatment in the future.

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Section: The Emerging Roles Of Rna Methylation As Critical Regulators...mentioning

confidence: 99%

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

Chen,

Liu,

Zhang

et al. 2024

Clinical & Translational Med

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“…For instance, Huang et al revealed that KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/MAPK pathway in an m6A-dependent manner. 15 Chen et al showed that silencing of m6A methyltransferase KIAA1429 inhibits the progression of NSCLC by promoting the p53 signaling pathway and ferroptosis. 16 Autophagy is an evolutionarily conserved intracellular degradation and metabolism process that plays important roles in maintaining cell metabolism, genome integrity, and organelles self-renewal.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, Huang et al. revealed that KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/MAPK pathway in an m6A‐dependent manner 15 . Chen et al.…”

Section: Introductionmentioning

confidence: 99%

The m6 RNA methylation regulator KIAA1429 is associated with autophagy‐mediated drug resistance in lung cancer

Ma,

Xiu,

Ding

2024

FASEB BioAdvances

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N6‐methyladenosine (m6A) modification plays a crucial role in cancer progression. However, the role of m6A modification‐mediated autophagy underlying non‐small cell lung cancer (NSCLC) gefitinib resistance remains unknown. Here, we discovered that m6A methyltransferase KIAA1429 was highly expressed in NSCLC gefitinib‐resistant cells (PC9‐GR) as well as tissues, and KIAA1429 high expression was associated with poor survival. In addition, silent KIAA1429 repressed gefitinib resistance in NSCLC and reduced tumor growth in vivo. Mechanistically, KIAA1429 stabilized WTAP, a significant player in autophagy, by binding to the 3′ untranslated regions (3′‐UTR) of WTAP. In a word, our findings indicated that KIAA1429 could elevate NSCLC gefitinib resistance, which may provide a promising targeted therapy for NSCLC patients.

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“…In mammalian cells, MAPK signaling is a fundamental mechanism, transmitting signals related to proliferation, apoptosis, and differentiation [13][14][15] . ERK, p38, JNK, and ERK5, which are a set of serinethreonine kinases conserved throughout evolution, serve as the classical MAPK pathways 16 .…”

Section: Introductionmentioning

confidence: 99%

Predicting Bladder Cancer Survival with High Accuracy: Insights from MAPK Pathway-related Genes

Cheng,

Li,

Zhou

et al. 2024

Preprint

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The mitogen-activated protein kinase (MAPK) pathway plays a critical role in tumor development and immunotherapy. Nevertheless, additional research is necessary to comprehend the relationship between the MAPK pathway and the prognosis of bladder cancer (BLCA), as well as its influence on the tumor immune microenvironment.To create prognostic models, we screened ten genes associated with the MAPK pathway using COX and least absolute shrinkage and selection operator (LASSO) regression analysis. These models were validated in the Genomic Data Commons (GEO) cohort and further examined for immune infiltration, somatic mutation, and drug sensitivity characteristics. Finally, the findings were validated using The Human Protein Atlas (HPA) database and through Quantitative Real-time PCR (qRT-PCR).Patients were classified into high-risk and low-risk groups based on the prognosis-related genes of the MAPK pathway. The high-risk group had poorer overall survival than the low-risk group and showed increased immune infiltration compared to the low-risk group. Additionally, the nomograms built using the risk scores and clinical factors exhibited high accuracy in predicting the survival of BLCA patients.The prognostic profiling of MAPK pathway-associated genes represents a potent clinical prediction tool, serving as the foundation for precise clinical treatment of bladder cancer.

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KIAA1429 promotes tumorigenesis and gefitinib resistance in lung adenocarcinoma by activating the JNK/ MAPK pathway in an m6A-dependent manner

Cited by 44 publications

References 48 publications

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

RNA methylation‐related inhibitors: Biological basis and therapeutic potential for cancer therapy

The m6 RNA methylation regulator KIAA1429 is associated with autophagy‐mediated drug resistance in lung cancer

Predicting Bladder Cancer Survival with High Accuracy: Insights from MAPK Pathway-related Genes

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