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Updated: Dec 30, 2025
Induction and Testing of Hypoxia in Cell Culture
Published on: August 12, 2011
Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response
Lin Huan1, Tianan Guo2, Yangjun Wu1
1Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Background:
Hypoxic tumors are refractory to DNA damage drugs. However, the underlying mechanism has yet to be elucidated. We aimed to identify lncRNAs that upregulated under hypoxia and their effects on colorectal cancer (CRC).
Methods:
CRC cells were treated with 1% O2 to identify lncRNAs that upregulated under hypoxia. We integrated these lncRNAs with RNA-seq of 4 paired CRC tissues and TCGA data to get candidate lncRNAs. Multiple in vitro and in vivo assays were used to explore the role of LUCAT1 in CRC.
Results:
We identified a hypoxia-induced lncRNA LUCAT1 that facilitated the growth of CRC cells and contributed to drug resistance of CRC cells both in vitro and in vivo. Mechanically, LUCAT1 interacts with polypyrimidine tract binding protein 1 (PTBP1) in CRC cells, facilitates the association of a set of DNA damage related genes with PTBP1, thus resulting in altered alternative splicing of these genes. Moreover, ectopic expression of PTBP1 in CRC cells with knockdown of LUCAT1 abrogated the effects induced by LUCAT1 knockdown. Chemotherapeutics drug combined with LUCAT1 knockdown via antisense oligonucleotides (ASO) would get a better outcome in vivo, compared with group treated with chemotherapeutic drug only. Notably, LUCAT1 is upregulated in CRC tissues, compared to adjacent normal tissues; and CRC patients with higher LUCAT1 have a worse prognosis and poorly responded to chemotherapy in the clinic.
Conclusions:
Our data suggested CRC cells utilizes LUCAT1 to develop resistance to DNA damage drugs, and disrupting the LUCAT1/PTBP1 axis might be a promising therapeutic strategy for refractory hypoxic tumors.
Insights
Hypoxia-induced long non-coding RNA LUCAT1 promotes colorectal cancer (CRC) growth and chemoresistance by regulating alternative splicing via the LUCAT1/PTBP1 axis. Targeting this pathway offers a new strategy for treating refractory hypoxic tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hypoxic tumors exhibit resistance to DNA damage drugs, but the mechanisms remain unclear.
- Identifying hypoxia-upregulated lncRNAs is crucial for understanding colorectal cancer (CRC) progression and drug resistance.
Purpose of the Study:
- To identify hypoxia-induced long non-coding RNAs (lncRNAs) in colorectal cancer (CRC).
- To investigate the role and mechanism of the identified lncRNA LUCAT1 in CRC growth and chemoresistance.
Main Methods:
- Hypoxia induction in CRC cells to identify upregulated lncRNAs.
- Integration of lncRNA data with RNA-seq and TCGA data to identify candidate lncRNAs.
- In vitro and in vivo assays to explore the function of LUCAT1 in CRC.
Main Results:
- A hypoxia-induced lncRNA, LUCAT1, was identified and found to promote CRC cell growth and drug resistance.
- LUCAT1 interacts with PTBP1, altering alternative splicing of DNA damage-related genes.
- LUCAT1 is upregulated in CRC tissues, correlating with poor prognosis and reduced chemotherapy response.
Conclusions:
- CRC cells use LUCAT1 to develop resistance to DNA damage drugs.
- Disrupting the LUCAT1/PTBP1 axis presents a potential therapeutic strategy for refractory hypoxic tumors.
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