KIAA1199 Expression Research Articles

Mechanism of the KIAA1429/KLF1/PD-L1 Axis in Regulating Immune Escape in Non-small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC), accounting for approximately 80% of lung cancer cases, remains the leading cause of cancer-related mortality. Immune evasion is a critical challenge in NSCLC, contributing to poor treatment outcomes. This study investigates the role of KIAA1429 in immune evasion, aiming to identify novel therapeutic targets and provide a theoretical basis for NSCLC treatment. NSCLC cell lines were cultured to assess the expression of KIAA1429, KLF transcription factor (KLF1), and programmed cell death ligand 1 (PD-L1). Co-culture experiments were conducted with peripheral blood mononuclear cells (PBMCs) to evaluate cytotoxicity, CD8+T cell proportions, and levels of interferon-gamma (IFN-γ)/interleukin (IL)-10/IL-2. Additionally, N6-methyladenosine (m6A) modification in NSCLC cells, m6A enrichment on KLF1, and KLF1 mRNA stability were analyzed. Results showed increased expression of KIAA1429 and KLF1 in NSCLC cells. Knockdown of KIAA1429 inhibited NSCLC cell proliferation, enhanced PBMC cytotoxicity and CD8+T cell activation, increased IFN-γ and IL-2 levels, and decreased IL-10 levels. Mechanistically, KIAA1429 stabilized KLF1 mRNA level through m6A modification, promoting both KLF1 and PD-L1 expression. Overexpression of KLF1 or PD-L1 reversed the immune-modulating effects of KIAA1429 knockdown. In conclusion, KIAA1429 facilitates immune evasion in NSCLC by stabilizing KLF1 mRNA and upregulating PD-L1 expression.

The m6A writer KIAA1429 regulates photoaging progression via MFAP4-dependent collagen synthesis

BackgroundN6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown.ObjectivesThis study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging.Methodsm6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay.Resultsm6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-bRII and upregulation of MMP1 in UVR-irradiated human dermal fibroblasts (HDFs). Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process.ConclusionsThe increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.

Silencing of KIAA1429, a N6-methyladenine methyltransferase, inhibits the progression of colon adenocarcinoma via blocking the hypoxia-inducible factor 1 signalling pathway.

KIAA1429 is an important 'writer' of the N6-methyladenine (m6A) modification, which is involved in tumour progression. This study was conducted to explore the mechanism of action of KIAA1429 in colon adenocarcinoma (COAD). KIAA1429-silenced COAD cell and xenograft tumour models were constructed, and the function of KIAA1429 was explored through a series of in vivo and in vitro assays. The downstream mechanisms of KIAA1429 were explored using transcriptome sequencing. Dimethyloxalylglycine (DMOG), an activator of HIF-1α, was used for feedback verification. The expression of KIAA1429 in COAD tumour tissues and cells was elevated, and KIAA1429 exhibited differential expression at different stages of the tumour. Silencing of KIAA1429 inhibited the proliferation, migration, and invasion of HT29 and HCT116 cells. The expression levels of NLRP3, GSDMD and Caspase-1 were decreased in KIAA1429-silenced HT29 cells, indicating the pyroptotic activity was inhibited. Additionally, KIAA1429 silencing inhibited the growth of tumour xenograft. Transcriptome sequencing and reverse transcription quantitative polymerase chain reaction revealed that after KIAA1429 silencing, the expression of AKR1C1, AKR1C2, AKR1C3 and RDH8 was elevated, and the expression of VIRMA, GINS1, VBP1 and ARF3 was decreased. In HT29 cells, KIAA1429 silencing blocked the HIF-1 signalling pathway, accompanied by the decrease in AKT1 and HIF-1α protein levels. The activation of HIF-1 signalling pathway, mediated by DMOG, reversed the antitumour role of KIAA1429 silencing. KIAA1429 silencing inhibits COAD development by blocking the HIF-1 signalling pathway.

Enhanced anti-tumor therapy for hepatocellular carcinoma via sorafenib and KIAA1199-siRNA co-delivery liposomes

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. Sorafenib (Sf) is currently the first-line treatment for HCC. However, due to the side effects and unsatisfied efficiency of Sf, it is urgent to combine different therapeutic agents to inhibit HCC progression and increase the therapeutic efficacy. Here, our study constructed a Sf and KIAA1199-siRNA co-loaded liposome Sf-Lp-KIAA, which was prepared by electrostatic interaction of KIAA1199-siRNA and Sf loaded liposome (Sf-Lp). The particle size, zeta potential, the in vitro cumulative release was investigated. The physical and chemical properties were characterized, and the inhibition of HepG2 growth and metastasis in vitro was investigated. The cellular uptake of the co-loaded liposome was significantly higher than that of free siRNA, and the drug/siRNA could be co-delivered to the target cells. Sf-Lp-KIAA could significantly inhibit the growth, migration, invasion and down-regulate KIAA1199 expression of HepG2 cells in vitro than that of single Sf treated group. In addition, the co-delivery liposome accumulated in the HepG2 subcutaneous tumor model and suppress tumor growth after systemic administration without induce obvious toxicity. The present study implied that the co-delivery of Sf and KIAA1199-siRNA through the co-loaded liposomes exerted synergistic antitumor effects on HCC, which would lay a foundation for HCC therapy in the future.

KIAA1429 promotes gastric cancer progression by destabilizing RASD1 mRNA in an m6A-YTHDF2-dependent manner

BackgroundKIAA1429, 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.MethodsThe 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.ResultsBoth 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.ConclusionsKIAA1429 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.

KIAA1429 regulates lung adenocarcinoma proliferation and metastasis through the PI3K/AKT pathway by modulating ARHGAP30 expression.

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. 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. 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. This study revealed the activation mechanism and pivotal function of KIAA1429 in LUAD tumor development, paving the way for molecular-based interventions for LUAD.

Transcription factor KLF9 inhibits the proliferation, invasion, and migration of pancreatic cancer cells by repressing KIAA1522.

Pancreatic cancer (PC) has a poor prognosis and high mortality. Kruppel-like factor 9 (KLF9), a transcription factor, is aberrantly expressed in various neoplasms. The current study sought to analyze the functional role of KLF9 in the proliferation, invasion, and migration of PC cells. The expression patterns of KLF9 and KIAA1522 in normal pancreatic cells (HPDE-C7) and PC cells (Panc 03.27, BxPc3, SW1990) were determined by real-time quantitative polymerase chain reaction and Western blot assay. After treatment of KLF9 overexpression, proliferation, invasion, and migration were evaluated by cell counting kit-8, 5-ethynyl-2'-deoxyuridine staining, and Transwell assays. The binding of KLF9 to the KIAA1522 promoter was analyzed by dual-luciferase assay and chromatin immunoprecipitation. The rescue experiment was conducted to analyze the role of KIAA1522. KLF9 was downregulated, while KIAA1522 was upregulated in PC cells. KLF9 overexpression mitigated the proliferation, invasion, and migration of PC cells. Enrichment of KLF9 led to inhibition of the KIAA1522 promoter and repressed KIAA1522 expression. KIAA1522 overexpression neutralized the inhibitory role of KLF9 in PC cell functions. KLF9 is enriched in the KIAA1522 promoter and negatively regulates KIAA1522 expression, thereby mitigating the proliferation, invasion, and migration of PC cells.

KIAA1429 facilitates metastasis via m6A-YTHDC1-dependent RND3 down-regulation in hepatocellular carcinoma cells

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.

Clinical Significance and Potential Mechanisms of the RNA Methyltransferase KIAA1429 in Osteosarcoma.

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.

KIAA0101 promotes cisplatin resistance through regulating cell apoptosis in lung cancer cells.

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.

KIAA1429 facilitates progression of hepatocellular carcinoma by modulating m6A levels in HPN

BackgroundMost N6-methyladenosine (m6A)-associated modulatory proteins are involved in the pathogenesis of various cancers. The roles of m6A-related genes in liver hepatocellular carcinoma (LIHC) and the associated mechanisms remain unknown. MethodsGEO and GEPIA2 databases were used to identify the m6A modification-related genes which were differentially expressed in LIHC and adjacent non-tumor tissues, and quantitative PCR was used to evaluate the expression of KIAA1429, a major m6A methyltransferase, in LIHC cells. The effect of KIAA1429 on the malignant phenotypes of LIHC cells was evaluated in vitro. The UALCAN, GEPIA, and GEO databases and western blotting assays were used to identify the target genes of KIAA1429. ResultsKIAA1429 expression was markedly elevated in LIHC tissues, and patients with LIHC who had high KIAA1429 expression had a worse prognosis than those who had low expression. KIAA1429 silencing attenuated LIHC metastasis and proliferation. KIAA142 regulates m6A levels in HPN to intensify LIHC progression. ConclusionOur study suggests a KIAA1429-HPN modulatory model based on m6A modifications, that offers insights into the occurrence and development of LIHC.

The Prognostic Significance of KIAA1522 Expression in Non-Small-Cell Lung Cancer Patients.

The majority of lung cancers belong to the non-small-cell lung cancer (NSCLC) category, which is linked to a high mortality rate despite significant progress in diagnosis and treatment. Therefore, there is a need for novel prognostic NSCLC biomarkers to improve prognosis which currently remains poor. Recent studies and analyses of gene expression data of NSCLC revealed that high expression of KIAA1522 was significantly associated with poor prognosis and decreased overall survival. We identified 98 patients who underwent radical curative surgical resections or metastasectomy for pulmonary adenocarcinoma and squamous cell carcinoma at our institution or the pathological diagnosis confirmed by our pathologists. Following the latest data, we utilized immunohistochemistry to assess the expression of KIAA1522 and investigated its association with various clinic-demographic parameters, pathological stages, recurrence rates, overall survival, and disease-free survival in patients who achieved complete remission. Notably, there were no significant differences in the expression profiles of KIAA1522 between adenocarcinoma and squamous cell carcinoma samples (p=0.6). Survival analysis was conducted using log-rank tests and a multivariate Cox proportional hazard model. Of the 98 samples, 54 (55.1%) exhibited high expression of KIAA1522, and patients with high KIAA1522 expression had a significantly shorter overall survival than the low-expression group (p=0.01). Multivariate Cox proportional hazard models in which metastatic patients were included revealed that along with older age, higher TNM stage (tumor, node, metastasis system), and Eastern Cooperative Oncology Group (ECOG) performance status, high expression of KIAA1522 served as an independent prognostic factor. A high expression profile was not significantly associated with relapses in those whose complete remission had been achieved. Still, those patients with high expression of KIAA1522 tended to exhibit a shorter disease-free survival rate. In conclusion, our findings suggest that KIAA1522 expression is an independent factor for predicting overall survival and may serve as a valuable prognostic indicator for relapse and disease-free survival in NSCLC patients.

Pan-cancer analysis and experimental validation revealed the m6A methyltransferase KIAA1429 as a potential biomarker for diagnosis, prognosis, and immunotherapy.

KIAA1429, also known as VIRMA (vir-like m6A methyltransferase associated), plays a crucial role in tumorigenesis by modulating the level of m6A methylation. Previous studies have reported the prevalent overexpression of KIAA1429 in multiple cancers, related to a poor prognosis. Nevertheless, the precise role of KIAA1429 in tumor progression and its impact on the immune response remains unclear. A differential analysis of KIAA1429 expression was performed across cancers using data from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. We evaluated the role of KIAA1429 in the diagnosis, prognosis, and immunotherapy of tumor patients using bioinformatics methods. In addition, we also analyzed the associations between KIAA1429 and DNA methylation, immunotherapy. RT-qPCR was used to study the expression levels of KIAA1429 mRNA in 11 cell lines. KIAA1429 is found to be overexpressed in 28 cancer types, but its expression is relatively low in patients with acute myeloid leukemia (LAML) and ovarian serous cystadenocarcinoma (OV). Moreover, KIAA1429 demonstrates a positive correlation with advanced stages of multiple cancers. Kaplan-Meier (KM) analysis suggested that patients with elevated KIAA1429 expression had shorter survival. Furthermore, KIAA1429 shows strong associations with DNA methylation, tumor-infiltrating immune cells (TIICs), and the tumor microenvironment (TME). RT-qPCR results indicated significantly higher expression of KIAA1429 in tumor cells compared to matched-normal cells. In summary, our work illustrates that KIAA1429 expression is positively connected with poor prognosis in multiple cancers. Moreover, KIAA1429 could serve as a diagnostic factor and a predictor of immune response for specific tumor types.

Development of Therapeutic Agent for Osteoarthritis via Inhibition of KIAA1199 Activity: Effect of Ipriflavone In Vivo.

This study aimed to clarify the effects of ipriflavone, which effectively reduces KIAA1199 activity, on osteoarthritis (OA) development and progression in an in vivo OA mouse model. The OA model mice were divided into the ipriflavone (200 mg/kg/day) group and the control group. OA onset and progression were evaluated with the Mankin score, and KIAA1199 expression and hyaluronan (HA) accumulation were analyzed by immunostaining. The molecular weight of HA in the cartilage tissue and serum HA concentration were analyzed by chromatography and competitive HA enzyme-linked immunoassay. The effects of ipriflavone on the bovine cartilage explant culture under the influence of IL-1β were also investigated. In the ipriflavone group, Safranin-O stainability was well-preserved, resulting in significant reduction of the Mankin score (p = 0.027). KIAA1199 staining positivity decreased and HA stainability was preserved in the ipriflavone group. The serum HA concentration decreased, and the molecular weight of HA in the cartilage tissue increased in the ipriflavone group. The results of the cartilage explant culture indicated that ipriflavone could reduce GAG losses and increase the molecular weight of HA. Thus, ipriflavone may have an inhibitory effect on OA development/progression. Ipriflavone could be a therapeutic drug for OA by targeting KIAA1199 activity.

KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway

BackgroundN6-methyladenosine (m6A) has been shown to participate in various essential biological processes by regulating the level of target genes. However, the function of m6A modification mediated by KIAA1429 [alias virus-like m6A methyltransferase-associated protein (VIRMA)] during the progression of diffuse large B-cell lymphoma (DLBCL) remains undefined.MethodsThe expression and clinical significance of KIAA1429 were verified by our clinical data. CRISPR/Cas9 mediated KIAA1429 deletion, and CRISPR/dCas9-VP64 for activating endogenous KIAA1429 was used to evaluate its biological function. RNA sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, luciferase activity assay, RNA stability experiments, and co-immunoprecipitation were performed to investigate the regulatory mechanism of KIAA1429 in DLBCL. Tumor xenograft models were established for in vivo experiments.ResultsDysregulated expression of m6A regulators was observed, and a novel predictive model based on m6A score was established in DLBCL. Additionally, elevated KIAA1429 expression was associated with poor prognosis of patients with DLBCL. Knockout of KIAA1429 repressed DLBCL cell proliferation, facilitated cell cycle arrest in the G2/M phase, induced apoptosis in vitro, and inhibited tumor growth in vivo. Furthermore, carbohydrate sulfotransferase 11 (CHST11) was identified as a downstream target of KIAA1429, which mediated m6A modification of CHST11 mRNA and then recruited YTHDF2 for reducing CHST11 stability and expression. Inhibition of CHST11 diminished MOB1B expression, resulting in inactivation of Hippo–YAP signaling, reprogramming the expression of Hippo target genes.ConclusionsOur results revealed a new mechanism by which the Hippo–YAP pathway in DLBCL is inactivated by KIAA1429/YTHDF2-coupled epitranscriptional repression of CHST11, highlighting the potential of KIAA1429 as a novel predictive biomarker and therapeutic target for DLBCL progression.

The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

Chronic myeloid leukemia (CML) is a common adult leukemia. Both the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor prognosis. The N6-methyladenine (m6A) modification plays an important regulatory role in various physiological and pathological processes. KIAA1429 is a known m6A regulator, but the biological role of KIAA1429 in CML is unclear. In this study, we observed that the m6A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase CML. Notably, KIAA1429 regulated the total level of RNA m6A modification in the CML cells and promoted the malignant biological behaviors of CML cells, including proliferation, migration, and imatinib resistance. Inhibiting KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m6A/YTHDF1 axis, consequently inhibiting CML proliferation and drug efflux, ultimately increasing the sensitivity of CML cells to imatinib. Moreover, the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their apoptosis. Rucaparib, a recently developed anti-cancer agent, suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell apoptosis. Rucaparib also inhibited the tumorigenesis of CML cells in vivo. The combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to imatinib. Our study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m6A/YTHDF1 axis to up-regulate RAB27B expression, thereby promoting CML progression. Rucaparib exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial-mesenchymal transition.

KIAA1199, a major glycosaminoglycan component of the extracellular matrix, was reported to induce a fibrosis-like process. However, the relationship between KIAA1199 and liver fibrosis remains unclear. The liver fibrosis mouse model was established with carbon tetrachloride (CCl4). Here, we found that KIAA1199 was upregulated in CCl4-induced liver fibrosis. The expression of KIAA1199 was also increased in TGF-β-stimulated LX-2 cells. To clarify the impact of KIAA1199 in hepatic stellate cells (HSCs), we downregulated the expression of KIAA1199 in LX-2 cells by RNA interference. Cell proliferation, apoptosis, and migration were determined by CCK-8, flow cytometry, and transwell assay. We found that KIAA1199 knockdown reduced the expression of fibrosis markers α-SMA and COL1A1. Depletion of KIAA1199 inhibited cell proliferation by downregulating cyclin B1 and cyclin D1 and promoted cell apoptosis by upregulating Bax and downregulating Bcl-2. Moreover, KIAA1199 knockdown decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression to inhibit the migration ability of LX-2 cells. Silencing KIAA1199 also suppressed the epithelial-mesenchymal transition phenomenon. Collectively, our study revealed that KIAA1199 knockdown alleviated the activation, proliferation, and migration of HSCs, while promoting apoptosis of HSCs, which suggests that KIAA1199 may be a potential regulator of liver fibrosis.

Poor Prognostic Biomarker KIAA1522 Is Associated with Immune Infiltrates in Hepatocellular Carcinoma.

The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.

KIAA1429 promotes infantile hemangioma regression by facilitating the stemness of hemangioma endothelial cells.

Infantile hemangiomas are common vascular tumors with a specific natural history. The proliferation and regression mechanism of infantile hemangiomas may be related to the multilineage differentiation ability of hemangioma stem cells, but the specific mechanism is not well elucidated. KIAA1429 is an N6 -methyladenosine methylation-related protein that can also exert its role in a methylation-independent manner. This study aims to explore the function of KIAA1429 in infantile hemangiomas. qRT-PCR, western blotting, and immunostaining were performed to verify the expression of KIAA1429. The endothelial and fibroblast-like phenotypes of hemangioma endothelial cells were detected after KIAA1429 knockdown and overexpression. The stemness properties of hemangioma endothelial cells and the underlying mechanism of KIAA1429 in hemangiomas were also investigated. Nude mouse models of infantile hemangiomas were conducted to ascertain the effects of KIAA1429 in vivo. The results showed that KIAA1429 was highly expressed in infantile hemangiomas, particularly in involuting hemangiomas. In vitro experiments confirmed that KIAA1429 inhibited the endothelial phenotype, enhanced the differentiation ability, and promoted the fibroblast-like phenotype of hemangioma endothelial cells by inducing endothelial cell transition to facultative stem cells. However, the effect of KIAA1429 on the potential target was shown to be independent of N6 -methyladenosine methylation modification. Mouse models further revealed that KIAA1429 could inhibit the proliferation and promote the regression of hemangiomas. In conclusion, this study found that KIAA1429 played an important role in the regression of infantile hemangiomas by enhancing the stemness of hemangioma endothelial cells and could be a potential treatment target for infantile hemangiomas.

Knockdown of LINC01138 protects human chondrocytes against IL-1β-induced damage by regulating the hsa-miR-1207-5p/KIAA0101 axis.

Long intergenic non-protein coding RNA 1138 (LINC01138) plays a vital role in human cancers. In this study, we aimed to investigate the effect of LINC01138 on the progression of osteoarthritis (OA) and explore its potential mechanism of action. The expression of LINC01138, hsa-miR-1207-5p, and KIAA0101 in OA tissues and normal tissues was analyzed using GSEA datasets and confirmed in human specimens. Human chondrocytes were treated with interleukin (IL)-1β to establish an OA cell model. Quantitative real time PCR(qRT-PCR), enzyme-linked immunosorbent assay, and western blotting analyses were performed to evaluate the role of LINC01138, hsa-miR-1207-5p, and KIAA0101 during extracellular matrix (ECM) protein degeneration and cellular inflammatory response. The target relationship was predicted using DIANA-TarBase and TargetScan. The binding effects were verified by dual-luciferase reporter assay. LINC01138 expression was higher in OA tissues than in normal controls. LINC01138 levels increased in chondrocytes treated with IL-1β. Silencing of LINC01138 attenuated the IL-1β-induced decrease in Col2α1, aggrecan, and sulphated glycosaminoglycan (sGAG), and inhibited the IL-1β-induced increase in matrix metalloproteinase (MMP)-13, IL-6, and tumor necrosis factor (TNF)-α. miR-1207-5p is weakly expressed in OA tissues and cell models. The inhibition of hsa-miR-1207-5p, a target of LINC01138, attenuated the effects of LINC01138 silencing on chondrocyte ECM degeneration and inflammatory responses. Silencing KIAA0101, a target of hsa-miR-1207-5p, alleviated the effect of hsa-miR-1207-5p on chondrocyte ECM degeneration and inflammatory responses. Furthermore, silencing of KIAA0101 inhibited the JAK/STATand Wnt signaling pathways. Silencing LINC01138 protected chondrocytes from IL-1β-induced damage, possibly by regulating the hsa-miR-1207-5p/KIAA0101 axis.