LNCcation: lncRNA localization and function

The Journal of Cell Biology, Journal Year: 2020, Volume and Issue: 220(2)

Published: Dec. 24, 2020

Subcellular localization of RNAs has gained attention in recent years as a prevalent phenomenon that influences numerous cellular processes. This is also evident for the large and relatively novel class long noncoding (lncRNAs). Because lncRNAs are defined RNA transcripts >200 nucleotides do not encode protein, they themselves functional units, making their subcellular critical to function. The discovery tens thousands cumulative evidence involving them almost every activity render assessment essential fully understanding biology. In this review, we summarize current knowledge lncRNA localization, factors controlling emerging themes, including role isoforms involvement phase separation bodies, implications on function behavior. We discuss gaps well opportunities these provide avenues investigation.

Language: Английский

---

Functions of N6-methyladenosine and its role in cancer

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: Dec. 1, 2019

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A installed by methyltransferases, removed demethylases recognized reader proteins, regulate RNA metabolism including translation, splicing, export, degradation microRNA processing. Alteration levels participates cancer pathogenesis development via expression tumor-related genes like BRD4, MYC, SOCS2 EGFR. In this review, we elaborate recent advances research enzymes. We also highlight underlying mechanism progression. Finally, review corresponding potential targets therapy.

Language: Английский

---

The potential role of RNA N6-methyladenosine in Cancer progression

Molecular Cancer, Journal Year: 2020, Volume and Issue: 19(1)

Published: May 12, 2020

Abstract N6-methyladenosine (m6A) is considered the most common, abundant, and conserved internal transcript modification, especially in eukaryotic messenger RNA (mRNA). m6A installed by methyltransferases (METTL3/14, WTAP, RBM15/15B, VIRMA ZC3H13, termed “writers”), removed demethylases (FTO, ALKBH5, ALKBH3, “erasers”), recognized m6A-binding proteins (YTHDC1/2, YTHDF1/2/3, IGF2BP1/2/3, HNRNP, eIF3, “readers”). Accumulating evidence suggests that methylation greatly impacts metabolism involved pathogenesis of many kinds diseases, including cancers. In this review, we focus on physiological functions modification its related regulators, as well potential biological roles these elements human tumors.

Language: Английский

---

The interplay between m6A RNA methylation and noncoding RNA in cancer

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Nov. 22, 2019

Abstract N6-methyladenosine (m6A) methylation, one of the most common RNA modifications, has been reported to execute important functions that affect normal life activities and diseases. Most studies have suggested m6A modification can complexity cancer progression by regulating biological related cancer. M6A noncoding RNAs regulates cleavage, transport, stability, degradation themselves. It also cell proliferation metastasis, stem differentiation, homeostasis in affecting function cells. Interestingly, play significant roles these modifications. Additionally, it is becoming increasingly clear potentially contribute clinical application treatment. In this review, we summarize effect interactions between modifications on involved progression. particular, discuss role as possible potential biomarkers therapeutic targets treatment cancers.

Language: Английский

---

Roles of METTL3 in cancer: mechanisms and therapeutic targeting

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Aug. 27, 2020

N6-methyladenosine (m6A) is the most abundant mRNA modification and catalyzed by methyltransferase complex, in which methyltransferase-like 3 (METTL3) sole catalytic subunit. Accumulating evidence recent years reveals that METTL3 plays key roles a variety of cancer types, either dependent or independent on its m6A RNA activity. While modifications have been extensively reviewed elsewhere, critical functions various types cancer, as well potential targeting treatment, not yet highlighted. Here we summarize our current understanding both oncogenic tumor-suppressive METTL3, underlying molecular mechanisms. The well-documented protein structure METTL3/METTL14 heterodimer provides basis for therapeutic targeting, also discussed this review.

Language: Английский

---

RETRACTED ARTICLE: m6A mRNA methylation initiated by METTL3 directly promotes YAP translation and increases YAP activity by regulating the MALAT1-miR-1914-3p-YAP axis to induce NSCLC drug resistance and metastasis

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: Dec. 9, 2019

Abstract Background METTL3 is an RNA methyltransferase that mediates m 6 A modification and implicated in mRNA biogenesis, decay, translation. However, the biomechanism through which regulates MALAT1-miR-1914-3p-YAP axis activity to induce NSCLC drug resistance metastasis not very clear. Methods The expression of was analyzed by qPCR assays. Protein levels were western blotting immunofluorescent staining. Cellular proliferation detected CCK8 Cell migration invasion wound healing transwell assays, respectively. Promoter activities gene transcription luciferase reporter Finally, MeRIP. Results increased YAP . METTL3, YTHDF3, YTHDF1, eIF3b directly promoted translation interaction with initiation machinery. Moreover, level MALAT1 due a higher mediated METTL3. Meanwhile, stability METTL3/YTHDF3 complex. Additionally, functions as competing endogenous sponges miR-1914-3p promote via YAP. Furthermore, reduction knockdown inhibits tumor growth enhances sensitivity DDP vivo. Conclusion indicated methylation initiated promotes recruiting YTHDF1/3 complex increases regulating axis. metastasis.

Language: Английский

---

M6A-mediated upregulation of LINC00958 increases lipogenesis and acts as a nanotherapeutic target in hepatocellular carcinoma

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Jan. 8, 2020

Long non-coding RNAs (lncRNAs) possess significant regulatory functions in multiple biological and pathological processes, especially cancer. Dysregulated lncRNAs hepatocellular carcinoma (HCC) their therapeutic applications remain unclear.Differentially expressed lncRNA profile HCC was constructed using TCGA data. LINC00958 expression level examined cell lines tissues. Univariate multivariate analyses were performed to demonstrate the prognostic value of LINC00958. Loss-of-function gain-of-function experiments used assess effects on proliferation, motility, lipogenesis. Patient-derived xenograft model established for vivo experiments. RNA immunoprecipitation, dual luciferase reporter, biotin-labeled miRNA pull-down, fluorescence situ hybridization, sequencing assays elucidate underlying molecular mechanisms. We developed a PLGA-based nanoplatform encapsulating siRNA evaluated its superiority systemic administration.We identified lipogenesis-related lncRNA, LINC00958, whose upregulated High independently predicted poor overall survival. Functional showed that aggravated malignant phenotypes vitro vivo. Mechanistically, sponged miR-3619-5p upregulate hepatoma-derived growth factor (HDGF) expression, thereby facilitating lipogenesis progression. METTL3-mediated N6-methyladenosine modification led upregulation through stabilizing transcript. A loaded with si-LINC00958 administration. This novel drug delivery system controlled release, tumor targeting, safe, presented satisfactory antitumor efficacy.Our results delineate clinical significance mechanisms involved progression, providing indicator promising nanotherapeutic target.

Language: Английский

---

The role of m6A, m5C and Ψ RNA modifications in cancer: Novel therapeutic opportunities

Molecular Cancer, Journal Year: 2021, Volume and Issue: 20(1)

Published: Jan. 18, 2021

Abstract RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programmes. Significant advances been made in understanding the functional role regulating coding and non-coding processing function, which turn thoroughly shape distinct They affect diverse biological processes, correct deposition many these is required for normal development. Alterations their are implicated several diseases, including cancer. In this Review, we focus on occurrence N 6 -methyladenosine (m A), 5-methylcytosine 5 C) pseudouridine (Ψ) RNAs describe physiopathological We will highlight latest insights into mechanisms how influence tumour development, maintenance, progression. Finally, summarize development small molecule inhibitors that target specific writers or erasers to rewind epitranscriptome a cancer cell therapeutic potential.

Language: Английский

---

The how and why of lncRNA function: An innate immune perspective

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Journal Year: 2019, Volume and Issue: 1863(4), P. 194419 - 194419

Published: Sept. 2, 2019

Language: Английский

---

Role of m6A RNA methylation in cardiovascular disease (Review)

International Journal of Molecular Medicine, Journal Year: 2020, Volume and Issue: 46(6), P. 1958 - 1972

Published: Oct. 6, 2020

N6‑methyladenosine (m6A) is the most prevalent and abundant type of internal post‑transcriptional RNA modification in eukaryotic cells. Multiple types RNA, including mRNAs, rRNAs, tRNAs, long non‑coding RNAs microRNAs, are involved m6A methylation. The biological function dynamically reversibly mediated by methyltransferases (writers), demethylases (erasers) binding proteins (readers). methyltransferase complex responsible for catalyzation typically made up methyltransferase‑like (METTL)3, METTL14 Wilms tumor 1‑associated protein. Erasers remove methylation fat mass obesity‑associated protein ALKB homolog 5. Readers play a role through recognition m6A‑modified targeted RNA. YT521‑B homology domain family, heterogeneous nuclear ribonucleoprotein insulin‑like growth factor 2 mRNA‑binding serve as readers. on transcripts plays pivotal regulation downstream molecular events functions, such splicing, transport, stability translatability at level. dysregulation associated with cancer, drug resistance, virus replication pluripotency embryonic stem Recently, number studies have identified aberrant cardiovascular diseases (CVDs), cardiac hypertrophy, heart failure, arterial aneurysm, vascular calcification pulmonary hypertension. aim present review article was to summarize recent research progress CVD give brief perspective its prospective applications CVD.

Language: Английский

---