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lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
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The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
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The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35.

Pei Y Liu1, Andrew E Tee1, Giorgio Milazzo2

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A novel long noncoding RNA, lncNB1, is highly expressed in neuroblastoma and promotes cancer growth by stabilizing the N-Myc oncoprotein. Targeting lncNB1 offers a potential therapeutic strategy for this aggressive childhood cancer.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Neuroblastoma, a common childhood cancer, often involves MYCN oncogene amplification and N-Myc oncoprotein overexpression.
  • High N-Myc levels are associated with poor patient prognosis and treatment resistance.

Purpose of the Study:

  • To identify novel molecular targets in MYCN-amplified neuroblastoma.
  • To investigate the role of the long noncoding RNA lncNB1 in neuroblastoma oncogenesis.

Main Methods:

  • RNA sequencing analysis of neuroblastoma cell lines and tissues.
  • lncNB1 knockdown experiments in vitro and in vivo.
  • Analysis of protein synthesis and gene transcription pathways.

Main Results:

  • lncNB1 is significantly overexpressed in MYCN-amplified neuroblastoma and across various cancers.
  • lncNB1 interacts with ribosomal protein RPL35 to boost E2F1 synthesis, driving DEPDC1B transcription.
  • DEPDC1B promotes ERK phosphorylation and N-Myc stabilization, crucial for neuroblastoma growth.
  • lncNB1 knockdown inhibits neuroblastoma cell growth and causes tumor regression in mice.
  • High lncNB1 and RPL35 levels correlate with poor patient outcomes.

Conclusions:

  • lncNB1 is a key driver of MYCN-driven neuroblastoma oncogenesis.
  • lncNB1 and RPL35 are essential for E2F1 synthesis and N-Myc stability.
  • lncNB1 represents a promising therapeutic target for neuroblastoma treatment.