Targeting IGF2BP3 in Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9423 - 9423

Published: May 29, 2023

RNA-binding proteins (RBPs) can regulate multiple pathways by binding to RNAs, playing a variety of functions, such as localization, stability, and immunity. In recent years, with the development technology, researchers have discovered that RBPs play key role in N6-methyladenosine (m6A) modification process. M6A methylation is most abundant form RNA eukaryotes, which defined on sixth N atom adenine RNA. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) one components m6A proteins, plays an important decoding marks performing various biological functions. IGF2BP3 abnormally expressed many human cancers, often associated poor prognosis. Here, we summarize physiological organisms describe its mechanism tumors. These data suggest may be valuable therapeutic target prognostic marker future.

Language: Английский

---

HKDC1 reprograms lipid metabolism to enhance gastric cancer metastasis and cisplatin resistance via forming a ribonucleoprotein complex

Cancer Letters, Journal Year: 2023, Volume and Issue: 569, P. 216305 - 216305

Published: July 7, 2023

Language: Английский

---

CircNFATC3 promotes the proliferation of gastric cancer through binding to IGF2BP3 and restricting its ubiquitination to enhance CCND1 mRNA stability

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 20, 2023

Abstract Background Insulin like growth factor II mRNA binding protein 3 (IGF2BP3) is an RNA with multiple roles in regulation of gene expression at the post-transcriptional level and implicated tumorigenesis progression numerous cancers including gastric cancer (GC). Circular RNAs (circRNAs) are a diverse endogenous noncoding population that have important regulatory cancer. However, circRNAs regulate IGF2BP3 GC largely unknown. Methods CircRNAs bound to were screened cells using immunoprecipitation sequencing (RIP-seq). The identification localization circular nuclear activated T (circNFATC3) identified Sanger sequencing, RNase R assays, qRT-PCR, nuclear-cytoplasmic fractionation RNA-FISH assays. CircNFATC3 human tissues adjacent normal measured by qRT-PCR ISH. biological role circNFATC3 was confirmed vivo vitro experiments. Furthermore, RIP, RNA-FISH/IF, IP rescue experiments performed uncover interactions between circNFATC3, cyclin D1 (CCND1). Results We GC-associated circRNA, interacted IGF2BP3. significantly overexpressed positively associated tumor volume. Functionally, proliferation decreased after knockdown vitro. Mechanistically, cytoplasm, which enhanced stability preventing ubiquitin E3 ligase TRIM25-mediated ubiquitination, thereby enhancing axis IGF2BP3-CCND1 promoting CCND1 stability. Conclusions Our findings demonstrate promotes stabilizing enhance Therefore, potential novel target for treatment GC.

Language: Английский

---

A novel peptide PDHK1-241aa encoded by circPDHK1 promotes ccRCC progression via interacting with PPP1CA to inhibit AKT dephosphorylation and activate the AKT-mTOR signaling pathway

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Feb. 15, 2024

Abstract Background Clear cell renal carcinoma (ccRCC) is the most prevalent kidney cancer with high aggressive phenotype and poor prognosis. Accumulating evidence suggests that circRNAs have been identified as pivotal mediators in cancers. However, role of ccRCC progression remains elusive. Methods The differentially expressed 4 paired human adjacent noncancerous tissues were screened using circRNA microarrays candidate target was selected based on expression level weighted gene correlation network analysis (WGCNA) omnibus (GEO) database. CircPDHK1 ( n = 148) evaluated along clinically relevant information. RT-qPCR, RNase R digestion, actinomycin D (ActD) stability test conducted to identify characteristics circPDHK1. subcellular distribution circPDHK1 analyzed by fractionation assay fluorescence situ hybridization (FISH). Immunoprecipitation-mass spectrometry (IP-MS) immunofluorescence (IF) employed evaluate protein-coding ability cells transfected siRNAs, plasmids or lentivirus approach, proliferation, migration invasion, well tumorigenesis metastasis nude mice assessed clarify functional roles its encoded peptide PDHK1-241aa. RNA-sequencing, western blot analysis, immunoprecipitation (IP) chromatin (ChIP) assays further underlying mechanisms regulated Results upregulated closely related WHO/ISUP stage, T distant metastasis, VHL mutation Ki-67 levels. had a internal ribosome entry site (IRES) novel Functionally, we confirmed PDHK1-241aa not promoted invasion ccRCC. Mechanistically, activated HIF-2A at transcriptional level. interacted PPP1CA, causing relocation PPP1CA nucleus. This thereby inhibited AKT dephosphorylation AKT-mTOR signaling pathway. Conclusions Our data indicated circPDHK1-encoded promotes interacting inhibit dephosphorylation. study provides insights into multiplicity highlights potential use therapeutic for

Language: Английский

---

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 9, 2024

Abstract Chronic wounds are a major complication in patients with diabetes. Here, we identify therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic preclinical models. We show that circCDK13 can stimulate the proliferation migration of human dermal fibroblasts epidermal keratinocytes by interacting insulin-like growth factor 2 mRNA binding protein 3 an N6-Methyladenosine-dependent manner enhance CD44 c-MYC expression. engineered sEVs overexpress local subcutaneous injection male db/db mouse streptozotocin-induced type I rats could accelerate wound healing skin appendage regeneration. Our study demonstrates delivery may present option for treatment.

Language: Английский

---

Comprehensive review of amino acid transporters as therapeutic targets

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 260, P. 129646 - 129646

Published: Jan. 23, 2024

Language: Английский

---

Emerging roles of circular RNAs in tumorigenesis, progression, and treatment of gastric cancer

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Feb. 27, 2024

Abstract With an estimated one million new cases reported annually, gastric cancer (GC) ranks as the fifth most diagnosed malignancy worldwide. The early detection of GC remains a major challenge, and prognosis worsens either when patients develop resistance to chemotherapy or radiotherapy metastasizes. precise pathogenesis underlying is not well understood, which further complicates its treatment. Circular RNAs (circRNAs), recently discovered class noncoding that originate from parental genes through “back-splicing”, have been shown play key role in various biological processes both eukaryotes prokaryotes. CircRNAs linked cardiovascular diseases, diabetes, hypertension, Alzheimer's disease, occurrence progression tumors. Prior studies established circRNAs crucial GC, impacting tumorigenesis, diagnosis, progression, therapy resistance. This review aims summarize how contribute tumorigenesis examine their roles development drug resistance, discuss potential biotechnological drugs, response therapeutic drugs microorganism GC.

Language: Английский

---

CircZBTB44 promotes renal carcinoma progression by stabilizing HK3 mRNA structure

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: April 27, 2023

Abstract CircZBTB44 (hsa_circ_0002484) has been identified to be upregulated in renal cell carcinoma (RCC) tissues, while its role and contribution RCC remain elusive. We confirmed the overexpression of circZBTB44 cells compared normal kidney HK-2. knockdown suppressed viability, proliferation, migration inhibited tumorigenesis xenograft mouse models. Heterogeneous Nuclear Ribonucleoprotein C (HNRNPC) Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) are two RNA binding proteins circZBTB44. HNRNPC facilitated translocation from nuclei cytoplasm via m6A modification, facilitating interaction IGF2BP3 cells. Furthermore, Hexokinase (HK3) expression by HK3 exerted oncogenic effects on malignant behaviors tumor growth. In co-culture with macrophages, promoted M2 polarization macrophages up-regulating HK3. summary, mediated up-regulate HK3, promoting proliferation vitro vivo . The results study shed new light targeted therapy RCC.

Language: Английский

---

Regulatory mechanisms and therapeutic implications of insulin-like growth factor 2 mRNA-binding proteins, the emerging crucial m⁶A regulators of tumors

Theranostics, Journal Year: 2023, Volume and Issue: 13(12), P. 4247 - 4265

Published: Jan. 1, 2023

Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) serve essential biological functions as post-transcriptional performers, participating in the acquisition or maintenance of tumor hallmarks due to their distinct protein structures.Emerging evidence indicates that IGF2BPs belong class III type RNA N 6 -methyladenosine (m A) modification readers, controlling stability, storage, localization, metabolism, and translation multiple vital bioprocesses, particularly tumorigenesis progression.Here, we discuss underlying regulatory mechanisms pathological which act m A readers context pathogenesis multidrug resistance.Furthermore, highlight potential drug targets clinical treatment.Hence, precise novel therapeutic approaches could be uncovered by targeting epigenetic heterogeneity.

Language: Английский

---

Helicobacter pylori upregulates circPGD and promotes development of gastric cancer

Journal of Cancer Research and Clinical Oncology, Journal Year: 2024, Volume and Issue: 150(2)

Published: Feb. 26, 2024

Abstract Purpose Helicobacter pylori ( H. ) has unique biochemical traits and pathogenic mechanisms, which make it a substantial cause of gastrointestinal cancers. Circular RNAs (circRNAs) have concurrently been identified as an important participating factor in the pathophysiology several different However, underlying processes putative interactions between circRNAs received very little attention. To address this issue, we explored interaction to investigate how they might jointly contribute occurrence development gastric cancer. Methods Changes circPGD expression were detected using qRT-PCR. Cell proliferation migration changes assayed by colony formation, CCK-8 assay transwell assay. Apoptosis was measured flow cytometry. Western blot conducted detect cell migration, apoptosis, inflammation-associated proteins. QRT-PCR used measure factors. Results We found that induced increased infected human cells facilitated cancer progression three ways promoting enhancing inflammatory response, inhibiting apoptosis. Conclusions CircPGD appears play role -related may thus be viable, novel target for therapeutic intervention.

Language: Английский

---