Related Experiment Video

Updated: Jun 20, 2025

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
09:58

Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models

Published on: December 9, 2016

13.7K

RNA splicing variants of the novel long non-coding RNA, CyKILR, possess divergent biological functions in non-small

Xiujie Xie, H Patrick Macknight, Amy L Lu

    Biorxiv : the Preprint Server for Biology
    |July 19, 2024
    PubMed

    Insights

    A novel long non-coding RNA, CyKILR, is overexpressed in non-small cell lung cancer (NSCLC). Its variants, CyKILRa and CyKILRb, exhibit opposing roles, with CyKILRa suppressing tumors and CyKILRb promoting them.

    Area of Science:

    • Oncology
    • Molecular Biology
    • Genetics

    Background:

    • The CDKN2A gene, encoding tumor suppressors p16INK4A and p14ARF, is frequently inactivated in non-small cell lung cancer (NSCLC).
    • Tumor suppressor STK11 (Liver kinase B1) also plays a critical role in cancer development.

    Purpose of the Study:

    • To characterize a novel long non-coding RNA (lncRNA) overexpressed in NSCLC cells with active CDKN2A.
    • To elucidate the distinct roles of CyKILR splice variants in NSCLC tumorigenesis.

    Main Methods:

    • Identification and naming of the lncRNA as CyKILR (Cyclin-Dependent Kinase Inhibitor 2A-regulated lncRNA).
    • Analysis of CyKILR splice variants (CyKILRa and CyKILRb) and their regulation by CDKN2A and STK11.
    • Functional studies using antisense RNA oligonucleotides and siRNA to downregulate CyKILR variants, followed by proliferation, migration, and survival assays.
    • Transcriptomics analysis to investigate the molecular mechanisms of CyKILRa and CyKILRb.

    Main Results:

    • CyKILR is overexpressed in NSCLC and its expression correlates with active wild-type CDKN2A and STK11 genes.
    • CyKILRa, a nuclear-localized variant, exhibits tumor-suppressive functions by enhancing apoptosis and suppressing cell cycle pathways.
    • CyKILRb, a cytoplasmic variant, displays oncogenic properties by inhibiting tumor suppressor microRNAs.

    Conclusions:

    • CyKILR, through its distinct splice variants CyKILRa and CyKILRb, plays a complex, dual role in NSCLC.
    • CyKILRa acts as a tumor suppressor, while CyKILRb functions as an oncogene, highlighting the intricate roles of lncRNAs in cancer.
    • These findings offer new insights into lncRNA-mediated regulation in cell signaling and tumorigenesis.

    More Related Videos

    Using the E1A Minigene Tool to Study mRNA Splicing Changes10:25

    Using the E1A Minigene Tool to Study mRNA Splicing Changes

    Published on: April 22, 2021

    4.9K
    A Reporter Based Cellular Assay for Monitoring Splicing Efficiency08:53

    A Reporter Based Cellular Assay for Monitoring Splicing Efficiency

    Published on: September 15, 2021

    2.7K

    Related Concept Videos

    RNA Splicing01:32

    RNA Splicing

    Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
    56.3K
    Alternative RNA Splicing02:18

    Alternative RNA Splicing

    Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
    There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
    21.1K
    lncRNA - Long Non-coding RNAs02:39

    lncRNA - Long Non-coding RNAs

    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...
    8.5K
    Ribosomal RNA Synthesis02:53

    Ribosomal RNA Synthesis

    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.
    Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
    13.2K
    Types of RNA01:20

    Types of RNA

    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 regulating 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.
    RNA Performs Diverse...
    5.7K
    Non-LTR Retrotransposons03:18

    Non-LTR Retrotransposons

    As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
    11.4K