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Updated: Jan 23, 2026
Global Identification of Co-Translational Interaction Networks by Selective Ribosome Profiling
Published on: October 7, 2021
Ribosome profiling analysis identified a KRAS-interacting microprotein that represses oncogenic signaling in
Wenli Xu1, Bing Deng1, Penghui Lin1
1MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory for Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
Abstract:
The roles of concealed microproteins encoded by long noncoding RNAs (lncRNAs) are gradually being exposed, but their functions in tumorigenesis are still largely unclear. Here, we identify and characterize a conserved 99-amino acid microprotein named KRASIM that is encoded by the putative lncRNA NCBP2-AS2. KRASIM is differentially expressed in normal hepatocytes and hepatocellular carcinoma (HCC) cells and can suppress HCC cell growth and proliferation. Mechanistically, KRASIM interacts and colocalizes with the KRAS protein in the cytoplasm of human HuH-7 hepatoma cells. More importantly, the overexpression of KRASIM decreases the KRAS protein level, leading to the inhibition of ERK signaling activity in HCC cells. These results demonstrate a novel microprotein repressor of the KRAS pathway for the first time and provide new insights into the regulatory mechanisms of oncogenic signaling and HCC therapy.
Insights
Researchers discovered KRASIM, a microprotein from the NCBP2-AS2 long noncoding RNA, that inhibits hepatocellular carcinoma (HCC) growth by targeting the KRAS pathway. This finding offers new therapeutic strategies for HCC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) can encode microproteins with unknown roles in cancer.
- The function of microproteins in tumorigenesis, particularly in hepatocellular carcinoma (HCC), remains largely unexplored.
Purpose of the Study:
- To identify and characterize novel microproteins involved in HCC.
- To elucidate the mechanism by which a newly identified microprotein, KRASIM, affects HCC cell growth and signaling pathways.
Main Methods:
- Identification and characterization of the microprotein KRASIM encoded by lncRNA NCBP2-AS2.
- Analysis of KRASIM expression in normal hepatocytes and HCC cells.
- Investigation of KRASIM's interaction with KRAS protein in HuH-7 hepatoma cells.
- Assessment of KRASIM's effect on KRAS protein levels and ERK signaling activity.
Main Results:
- A conserved microprotein, KRASIM, was identified, encoded by the lncRNA NCBP2-AS2.
- KRASIM expression is altered in HCC cells and suppresses HCC cell growth and proliferation.
- KRASIM interacts with and colocalizes with KRAS in the cytoplasm.
- Overexpression of KRASIM reduces KRAS protein levels and inhibits ERK signaling in HCC cells.
Conclusions:
- KRASIM acts as a novel microprotein repressor of the KRAS pathway.
- This study reveals new insights into the regulation of oncogenic signaling in HCC.
- KRASIM presents a potential therapeutic target for HCC treatment.
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