CERS6 antisense RNA 1 promotes colon cancer via upregulating mitochondrial calcium uniporter
Juan Yu1, Xiaoguang Chen1, Jing Li1
1Endoscopic Diagnosis and Treatment Center, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
Background:
Colon cancer (CC) belongs to a common cancer of digestive system. Long non-coding RNAs (lncRNAs) are dysregulated in numerous cancers and affect their development. The function of lncRNA CERS6 antisense RNA 1 (CERS6-AS1) in CC remains unclear.
Materials And Methods:
CERS6-AS1 expression in colon adenocarcinoma tissues and CC cell lines was assessed by The Cancer Genome Atlas database and quantitative real-time polymerase chain reaction analysis. The function of CERS6-AS1 in CC was analysed by 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labelling, wound healing, Transwell and immunofluorescence assays. Mechanistic analyses including RNA pull down, RNA-binding protein immunoprecipitation and luciferase reporter assay revealed the interaction between RNAs.
Results:
CERS6-AS1 expression was aberrantly upregulated in colon adenocarcinoma tissues and CC cell lines. CERS6-AS1 knockdown inhibited CC cell malignant phenotypes and in vivo tumour growth. CERS6-AS1 served as the competing endogenous RNA of microRNA-16-5p in CC, and microRNA-16-5p inhibition partly rescued the effects of CERS6-AS1 depletion on CC development. Mitochondrial calcium uniporter was targeted by microRNA-16-5p. Mitochondrial calcium uniporter upregulation completely remedied the influence of CERS6-AS1 silencing in CC progression. Moreover, CERS6-AS1 enhanced the stability of mitochondrial calcium uniporter messenger RNA via recruiting RNA-binding protein embryonic lethal abnormal vision like 1.
Conclusion:
CERS6-AS1 promotes the development of CC via upregulating mitochondrial calcium uniporter expression.
Insights
Long non-coding RNA CERS6 antisense RNA 1 (CERS6-AS1) promotes colon cancer (CC) development by upregulating mitochondrial calcium uniporter. This study clarifies the role of CERS6-AS1 in CC progression.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- Colon cancer (CC) is a prevalent digestive system malignancy.
- Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
- The specific function of lncRNA CERS6 antisense RNA 1 (CERS6-AS1) in CC pathogenesis was previously undefined.
Purpose of the Study:
- To investigate the expression and functional role of CERS6-AS1 in colon cancer.
- To elucidate the molecular mechanism by which CERS6-AS1 influences CC progression.
Main Methods:
- Assessed CERS6-AS1 expression using The Cancer Genome Atlas and quantitative real-time polymerase chain reaction.
- Evaluated CC cell function and tumor growth via in vitro and in vivo assays.
- Utilized RNA pull down, RNA-binding protein immunoprecipitation, and luciferase reporter assays to determine molecular interactions.
Main Results:
- CERS6-AS1 was significantly upregulated in colon adenocarcinoma tissues and cell lines.
- CERS6-AS1 knockdown suppressed CC cell malignancy and tumor growth.
- CERS6-AS1 acts as a competing endogenous RNA for microRNA-16-5p, targeting mitochondrial calcium uniporter (MCU) and enhancing MCU mRNA stability via the RNA-binding protein embryonic lethal abnormal vision like 1.
Conclusions:
- CERS6-AS1 promotes colon cancer development.
- The mechanism involves the upregulation of mitochondrial calcium uniporter expression.
- CERS6-AS1 represents a potential therapeutic target for colon cancer.
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