Related Experiment Video

Updated: Jun 26, 2025

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

12.9K

The truncated AXIN1 isoform promotes hepatocellular carcinoma metastasis through SRSF9-mediated exon 9 skipping

Qian-Qian Zhang1, Ying-Shuang Miao2, Jun-Yi Hu2

  • 1State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Genomic Medicine, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, China.

Molecular and Cellular Biochemistry
|May 15, 2024
PubMed

Insights

Alternative splicing of Axis inhibitor protein 1 (AXIN1) impacts hepatocellular carcinoma (HCC) metastasis. AXIN1-S promotes HCC metastasis by activating the Wnt pathway, while AXIN1-L inhibits it, offering potential therapeutic targets.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cancer Research

Background:

  • Axis inhibitor protein 1 (AXIN1) is a known tumor suppressor involved in cancer development.
  • Alternative splicing of AXIN1 may play a role in hepatocellular carcinoma (HCC) progression.
  • Understanding the molecular mechanisms linking AXIN1 splicing to HCC metastasis is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the molecular mechanisms connecting AXIN1 alternative splicing to HCC metastasis.
  • To elucidate the role of the AXIN1 exon 9 splice isoform and SRSF9 in HCC cell migration and invasion.
  • To evaluate AXIN1 isoforms and SRSF9 as potential prognostic and therapeutic targets for HCC.

Main Methods:

  • Transcriptome sequencing, RT-PCR, qPCR, and Western blotting were used to analyze AXIN1 expression in HCC tissues and cells.
  • Wound healing and Transwell assays assessed the impact of AXIN1 isoforms and SRSF9 on HCC cell migration and invasion.
  • RNA immunoprecipitation, UV crosslinking, and RNA pulldown assays investigated the interaction between SRSF9 and AXIN1.

Main Results:

  • AXIN1-L (exon 9 included) was downregulated, while AXIN1-S (exon 9 skipped) was upregulated in HCC.
  • SRSF9 promotes AXIN1-S production by interacting with AXIN1 exons 8 and 10.
  • AXIN1-S enhanced HCC cell migration and invasion via Wnt pathway activation, whereas AXIN1-L had opposing effects. In vivo studies confirmed AXIN1-L inhibited metastasis, and SRSF9 promoted it.

Conclusions:

  • AXIN1 alternative splicing, specifically the balance between AXIN1-L and AXIN1-S, significantly influences HCC metastasis.
  • SRSF9 acts as an oncogene in HCC by promoting the pro-metastatic AXIN1-S isoform.
  • Targeting the AXIN1/Wnt/β-catenin signaling axis through modulation of AXIN1 isoforms presents a promising therapeutic strategy for HCC.
Keywords:
Alternative splicingAxis inhibition protein 1 (AXIN1)Hepatocellular carcinomaInvasionSerine and arginine-rich splicing factor 9 (SRSF9)

More Related Videos

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs10:32

Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs

Published on: December 19, 2019

10.8K
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

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
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
6.2K
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon...
3.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.5K
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...
11.5K