BACKGROUND: KIAA1429, a regulatory subunit of the N6-methyladenosine (m6A) methyltransferase complex, has been implicated in the progression of various cancers. However, the role of KIAA1429 in gastric cancer (GC) and its underlying mechanisms remain elusive. This study aimed to investigate the role of KIAA1429 in GC and to elucidate the underlying mechanisms.
METHODS: The expression patterns and clinical relevance of KIAA1429 in GC were assessed using quantitative real-time PCR (qRT-PCR), Western blotting, immunohistochemistry (IHC), and bioinformatic analysis. In vitro and in vivo loss- and gain-of-function assays, m6A dot blot assays, methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA-seq, MeRIP-qPCR, dual luciferase reporter assays, RNA stability assays, RNA immunoprecipitation (RIP) assays, and RNA pull-down assays were performed to investigate the biological functions and underlying molecular mechanisms of KIAA1429 in GC.
RESULTS: Both the mRNA and protein expression of KIAA1429 were greater in GC tissues than in normal gastric tissues. High KIAA1429 expression correlated positively with poor prognosis in GC patients. KIAA1429 not only promoted GC cell proliferation, colony formation, G2/M cell cycle transition, migration, and invasion in vitro but also enhanced GC tumor growth and metastasis in vivo. Mechanistically, KIAA1429 increased the m6A level of RASD1 mRNA and enhanced its stability in an m6A-YTHDF2-dependent manner, thereby upregulating its expression. RASD1 knockdown partially rescued the KIAA1429 knockdown-induced impairment of pro‑oncogenic ability in GC cells. The expression levels of KIAA1429 and RASD1 were negatively correlated in GC tissues.
CONCLUSIONS: KIAA1429 plays a pro‑oncogenic role in GC by downregulating RASD1 expression through destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner. KIAA1429 may serve as a prognostic biomarker and therapeutic target for GC.

BACKGROUND: Alterations in epigenetic factors are recognized as key contributors to the emergence of human cancer. The active and reversible alteration of N6-methyladenosine (m6A) RNA is crucial for controlling gene activity and determining cellular destiny. Even with these insights, the triggering of KIAA1429 (also called VIRMA) and its role in lung adenocarcinoma (LUAD) is mostly unclear. As a result, the objective of this study was to elucidate how KIAA1429 contributes to cancer development in LUAD.
METHODS: This study utilized multiple methods for investigation, encompassing the in vitro functional examination of KIAA1429 in lung adenocarcinoma cells, transcriptome sequencing, methylation RNA immunoprecipitation sequencing (MeRIP-seq), as well as RNA stability tests to ascertain the half-life and stability of the target genes.
RESULTS: The results indicated that modifying the expression of KIAA1429 regulated the proliferation and metastasis of LUAD. By employing transcriptome sequencing alongside MeRIP-seq analysis, the research pinpointed genes affected by m6A alterations triggered by KIAA1429. In a more detailed manner, it was discovered that KIAA1429 plays a regulatory role in the expression of ARHGAP30. Suppressing KIAA1429 results in reduced m6A levels in the mRNA of the target gene ARHGAP30, boosting its stability and expression, thus inhibiting tumor proliferation and metastasis.
CONCLUSIONS: This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.

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.

BACKGROUND: Inhibin A and N6-methyladenosine methylation modifications participate in oral squamous cell carcinoma development. However, the N6-methyladenosine modification of Inhibin A in oral squamous cell carcinoma has not been revealed. This study reveals a key gene \"Inhibin A\" that may affect the tumorigenesis of oral squamous cell carcinoma and its molecular mechanisms on N6-methyladenosine methyltransferase KIAA1429-mediated N6-methyladenosine methylation modification.
METHODS: Bioinformatics analysis and quantitative real-time polymerase chain reaction identified the potential regulatory genes in oral squamous cell carcinoma. We examined the changes in the proliferation (Cell Counting Kit-8 assay), migration (transwell migration assay), and invasion (transwell invasion assays) of oral squamous cell carcinoma cells. We performed a xenograft tumor experiment to validate the role of Inhibin A in oral squamous cell carcinoma in vivo. The interactions between Inhibin A and KIAA1429 were analyzed using bioinformatics, methylated RNA immunoprecipitation-qPCR, quantitative real-time polymerase chain reaction, and Western blotting experiments.
RESULTS: Inhibin A had the highest expression in patients with oral squamous cell carcinoma. Inhibin A silencing impaired the ability of oral squamous cell carcinoma cells to proliferate, migrate, and invade, as well as limited the tumorous growth of oral squamous cell carcinoma cells in vivo. Bioinformatics analysis showed that Inhibin A expression positively interacted with KIAA1429 expression in The Cancer Genome Atlas database. The levels were also upregulated in our clinical samples. Furthermore, KIAA1429 silencing repressed the N6-methyladenosine level of Inhibin A in oral squamous cell carcinoma.
CONCLUSIONS: Inhibin A promotes the tumorigenesis of oral squamous cell carcinoma by KIAA1429-mediated N6-methyladenosine modification. This study adds to our current knowledge of the molecular mechanisms underlying oral squamous cell carcinoma malignancy.

UNASSIGNED: N6-methyladenosine (m6A) modification has been associated with non-small cell lung cancer (NSCLC) tumorigenesis.
UNASSIGNED: This study aimed to determine the functions of Vir-like m6A methyltransferase-associated (KIAA1429) and relaxin family peptide receptor 1 (RXFP1) in NSCLC.
UNASSIGNED: A quantitative real-time polymerase chain reaction was used to analyze the mRNA levels of KIAA1429 and RXFP1 in NSCLC. After silencing KIAA1429 or RXFP1 in NSCLC cells, changes in the malignant phenotypes of NSCLC cells were assessed using cell counting kit-8, colony formation, and transwell assays. Finally, the m6A modification of RXFP1 mediated by KIAA1429 was confirmed using luciferase, methylated RNA immunoprecipitation, and western blot assays.
UNASSIGNED: KIAA1429 and RXFP1 were upregulated and downregulated in NSCLC, respectively. Silencing of KIAA1429 attenuated the viability, migration, and invasion of NSCLC cells, whereas silencing of RXFP1 showed the opposite function in NSCLC cells. Moreover, RXFP1 expression was inhibited by KIAA1429 via m6A-modification. Therefore, silencing RXFP1 reversed the inhibitory effect of KIAA1429 knockdown in NSCLC cells.
UNASSIGNED: Our findings confirmed that the KIAA1429/RXFP1 axis promotes NSCLC tumorigenesis. This is the first study to reveal the inhibitory function of RXFP1 in NSCLC via KIAA1429-mediated m6A-modification. These findings may help identify new biomarkers for targeted NSCLC therapy.

N6-methyladenosine (m6A), a dynamically reversible modification in eukaryotic RNAs, modulates gene expression and pathological processes in various tumors. KIAA1429, the largest component of the m6A methyltransferase complex, plays an important role in m6A modification. However, the underlying mechanism of KIAA1429 in hepatocellular carcinoma (HCC) remains largely unknown. Immunohistochemical assay was performed to examine the expression of KIAA1429 in HCC tissues. Transwell, wound healing and animal experiments were used to investigate the influence of KIAA1429 on cell migration and invasion. The mRNA high-throughput sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed to screen the downstream target of KIAA1429. RNA stability assays, RNA immunoprecipitation assay (RIP), MeRIP-qPCR and luciferase assay were used to evaluate the relationship between KIAA1429 and the m6A-modified genes. Results showed that the expression level of KIAA1429 was significantly higher in HCC tissues than in adjacent tissues, and the upregulation of KIAA1429 could promote HCC metastasis in vitro and in vivo. Mechanistically, we confirmed that KIAA1429 negatively regulated the tumor suppressor, Rho family GTPase 3 (RND3), by decreasing its mRNA stability in coordination with the m6A reader YTHDC1. Moreover, we demonstrated that KIAA1429 could regulate the m6A modification of RND3 mRNA via its RNA binding domain. Our data indicated that KIAA1429 exerted its oncogenic role by inhibiting RND3 expression in an m6A-dependent manner, suggesting that KIAA1429 might be a potential prognostic biomarker and therapeutic target in HCC.

Background: KIAA1429, a member of the RNA methyltransferase complex, is involved in cancer progression; however, the clinical significance and underlying mechanism of KIAA1429 in osteosarcoma (OS) remains to be reported. Methods: We evaluated the clinical significance of KIAA1429 in OS by performing RT-qPCR, microarray, and RNA sequencing and using published data as a reference. Two KIAA1429-targeting siRNA constructs were transfected into SW1353 cells. CCK-8 assay, colony formation assays, flow cytometry and the xenograft mouse model were conducted to investigate the biological function of KIAA1429 in OS. Results: The mRNA expression of KIAA1429 was markedly upregulated in 250 OS samples as compared to that in 71 non-cancer samples (standardized mean difference = 0.67). Summary receiver operating characteristic curve analysis revealed that KIAA1429 exhibited reliable diagnostic capacity to differentiate OS samples from non-cancer samples (area under the curve = 0.83). Further, survival analysis indicated that KIAA1429 overexpression was associated with shorter overall survival time. Knocking down KIAA1429 reduced m6A methylation levels, inhibited proliferation, prevented the growth of tumors in vivo and accelerated apoptosis of OS cells. In total, 395 KIAA1429-related genes were identified among co-expressed genes and differentially expressed genes, which were enriched in the cell cycle pathway. Protein-protein interaction network analysis showed that CDK1, CCNA2, and CCNB1 were KIAA1429-related genes, serving as major network hubs in OS. Conclusions: Our findings indicate that KIAA1429 plays an oncogenic role in OS and potentially facilitates OS progression via a mechanism that involves regulating CDK1, CCNA2, and CCNB1.

Long non-coding RNAs (lncRNAs) are participated in tumourigenesis, including colorectal cancer (CRC). However, the effects and mechanisms of lncRNA POU6F2-AS1 in CRC have not been investigated. KIAA1429 act as a member of N6-methyladenosine (m6A) modification, has been knew as an oncogenic factor in various cancer containing CRC. We focus to investigate the regulation effect of lncRNA POU6F2-AS1, and the mechanism among lncRNA POU6F2-AS1 and KIAA1429 in CRC. The lncRNA POU6F2-AS1 and KIAA1429 levels in CRC tissue samples as well as cells were clarified by qRT-PCR, and their relationship was predicted by bioinformatics, MeRIP and Pearson analysis. Cell survival, migration and invasion were analyzed via EdU, wound healing and Transwell assays after lncRNA POU6F2-AS1 was down-regulated and KIAA1429 was up-regulated. LncRNA POU6F2-AS1 and KIAA1429 were enriched in CRC tissue samples. LncRNA POU6F2-AS1 silencing suppressed CRC cell survival, migration, and invasion, and KIAA1429 overexpression facilitated CRC cell malignancy. KIAA1429 promoted lncRNA POU6F2-AS1 expression via m6A modification. Furthermore, KIAA1429 upregulation reversed the inhibitory effect of lncRNA POU6F2-AS1 interference on the malignant behavior of CRC cells. lncRNA POU6F2-AS1 was modulated by KIAA1429 in the form of m6A modification to regulate the malignant phenotype of CRC, which may provide new insights into the potential application of KIAA1429-m6A-lncRNA POU6F2-AS1-based CRC therapy.

UNASSIGNED: Lung adenocarcinoma (LUAD) is the most common lung cancer worldwide. N6-methyladenosine (m6A) methylation is a messenger RNA (mRNA) modification that plays a key role in tumor growth, immune microenvironment, and immunotherapy response. This study investigated the expression level, mutation status, prognostic value, and predictive ability for response to anti-PD-1 immunotherapy of the m6A methyltransferase KIAA1429 in LUAD.
UNASSIGNED: This study examined multiple public data cohorts and independent samples from National Cancer Center (NCC) to evaluate the clinical significance and prognostic value of KIAA1429 in LUAD using bioinformatics techniques and immunohistochemical staining. We also evaluated the predictive value of KIAA1429 expression for anti-PD-1 immunotherapy efficacy. GSEA analysis was performed using KIAA1429 RNA-seq data at the tumor tissue level and cellular level to explore the potential molecular mechanism.
UNASSIGNED: In public databases, KIAA1429 was significantly associated with clinicopathological parameters in LUAD patients and had the potential to predict patient prognosis. The mutation characteristics of KIAA1429-related genes were analyzed and TP53, TTN, CSMD3, and other genes showed high mutation frequencies in LUAD. An independent cohort of 415 samples confirmed that high KIAA1429 expression was significantly associated with poorer prognosis in LUAD patients. Analysis of a small immunotherapy cohort showed that patients with high expression of KIAA1429 had better response after immunotherapy, and the proportion of patients with immunotherapy response was higher in this group.
UNASSIGNED: Our study confirmed that KIAA1429 was highly expressed in LUAD and was significantly associated with poor prognosis. Moreover, KIAA1429 may serve as a potential marker to predict the efficacy of immunotherapy in LUAD.

KIAA1429, an important component of the N6-methyladenine methyltransferase complex, is involved in the pathology of many types of cancer. In this study, the mechanisms through which KIAA1429 promotes non-small cell lung cancer (NSCLC) progression were explored using in vitro and in vivo experiments. Additionally, bioinformatics analysis of publicly available data was used to determine the relationship between KIAA1429 expression and NSCLC patient survival. The results showed that KIAA1429 was upregulated in NSCLC tissues and cells, and its high expression level was associated with low overall survival. Transcriptome analysis of KIAA1429-silenced NSCLC cells identified 346 differentially expressed genes, which were enriched in ferroptosis and the p53 signaling pathway. KIAA1429 silencing using small interfering (si) RNA promoted erastin-induced ferroptosis in NSCLC cells and activated the p53 signaling pathway. Moreover, si-KIAA1429 inhibited the proliferative, migratory, and invasive abilities of NSCLC cells in vitro and tumor growth in vivo. These in vitro effects were weakened by pifithrin-μ, a p53 inhibitor. Therefore, given its effects on ferroptosis and the p53 signaling pathway, targeting KIAA1429 could be an effective strategy for treating NSCLC.