Alternative splice variant of actinin-4 in small cell lung cancer

Kazufumi Honda1, Tesshi Yamada, Masahiro Seike

  • 1Cancer Proteomics Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

Oncogene
|May 4, 2004
PubMed

Insights

Researchers discovered a new actinin-4 RNA splice variant specific to small cell lung cancer (SCLC). This variant may serve as a diagnostic marker and therapeutic target for SCLC.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Alternative RNA splicing is crucial in cancer development.
  • Actinin-4 plays a role in cytoskeleton organization.
  • Specific splice variants can serve as biomarkers.

Purpose of the Study:

  • To identify novel RNA splice variants in small cell lung cancer (SCLC).
  • To investigate the expression and potential function of a newly identified actinin-4 splice variant in SCLC.

Main Methods:

  • RNA sequencing and variant analysis.
  • Expression profiling in SCLC cell lines and patient biopsies.
  • Protein characterization and localization studies.

Main Results:

  • A novel actinin-4 splice variant was identified and highly expressed in SCLC.
  • The variant expression was specific to SCLC and testis tissues.
  • The variant protein exhibited altered actin binding and localization.

Conclusions:

  • The alternatively spliced actinin-4 variant is a potential diagnostic marker for SCLC.
  • This variant represents a candidate target for novel SCLC therapies.

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...
Actin Polymerization and Cell Motility01:13

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate.
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...
Introduction to Actin01:26

Introduction to Actin

Actin is a highly conserved cytoskeletal protein found abundantly in eukaryotic cells. It constitutes 10% weight of the total cellular protein in muscle cells, while in non-muscle cells, it is lower and makes up around 1–5 percent of the total cell protein. Actin found in the unicellular amoebae and complex multicellular animals is around 80% similar, demonstrating their conservation over a billion years of evolution.  Actin coding genes are conserved within species and across different species.
Actin Filament Depolymerization01:19

Actin Filament Depolymerization

Actin filaments (F-actin) are composed of actin subunits. The dissociation of actin monomers can occur from either end of F-actin. The rate of dissociation is faster from the minus-end or the pointed end, where the actin subunits exist with a bound ADP, together known as ADP-actin. The depolymerization of F-actin is aided by proteins, including the actin-depolymerizing factor (ADF) and cofilin family of proteins, gelsolin, and glia maturation factor (GMF).
In F-actin, the ADF/cofilin proteins...
Generation of Straight or Branched Actin Filaments01:14

Generation of Straight or Branched Actin Filaments

The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...