miR-16 promotes the apoptosis of human cancer cells by targeting FEAT
Hongwei Liang1, Zheng Fu1, Xueyuan Jiang1,2
1Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu, 210093, China.
Background:
Although human cancers have heterogeneous combinations of altered oncogenes, some crucial genes are universally dysregulated in most cancers. One such gene, FEAT (faint expression in normal tissues, aberrant overexpression in tumors), is uniformly overexpressed in a variety of human cancers and plays an important role in tumorigenesis by suppressing apoptosis. However, the precise molecular mechanism through which FEAT is upregulated during tumorigenesis remains largely unknown.
Methods:
In this study, we used bioinformatic analyses to search for miRNAs that potentially target FEAT. We examined the expression of FEAT protein level by western blotting and miR-16 level by qRT-PCR assay. Cancer cell lines (A549, MCF-7 and Huh-7) with miR-16 upregulation and FEAT silencing were established and the effects on apoptosis of cancer cells in vitro were assessed. Luciferase reporter assay was also performed to investigate the interaction between miR-16 and FEAT.
Results:
We identified a specific target site for miR-16 in the 3'-untranslated region (3'-UTR) of FEAT. Consistent with the bioinformatic analyses, we identified an inverse correlation between the miR-16 and FEAT protein levels in lung cancer, breast cancer, and hepatocellular cancer tissues. We then experimentally validated miR-16 as a direct regulator of FEAT using cell transfection and luciferase assays. Finally, we demonstrated that the repression of FEAT by miR-16 promoted the apoptosis of cancer cells.
Conclusions:
Our findings provide the first clues regarding the role of miR-16 as a tumor suppressor in cancer cells through the inhibition of FEAT translation.
Insights
MicroRNA-16 (miR-16) suppresses tumor growth by directly inhibiting FEAT (faint expression in normal tissues, aberrant overexpression in tumors) translation. This study reveals miR-16 as a novel tumor suppressor targeting FEAT in various cancers.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- FEAT (faint expression in normal tissues, aberrant overexpression in tumors) is overexpressed in many cancers, promoting tumorigenesis by inhibiting apoptosis.
- The molecular mechanisms driving FEAT upregulation in cancer remain largely unknown.
Purpose of the Study:
- To investigate the molecular mechanisms regulating FEAT expression in cancer.
- To identify microRNAs (miRNAs) that target FEAT.
- To explore the role of miR-16 in cancer cell apoptosis via FEAT regulation.
Main Methods:
- Bioinformatic analysis to predict miRNA targets of FEAT.
- Western blotting and qRT-PCR to assess FEAT and miR-16 expression.
- Cancer cell line experiments (transfection, apoptosis assays) and luciferase reporter assays to validate miR-16 and FEAT interaction.
Main Results:
- A specific binding site for miR-16 was identified in the 3'-UTR of FEAT.
- An inverse correlation between miR-16 and FEAT protein levels was observed in lung, breast, and liver cancer tissues.
- miR-16 directly represses FEAT translation, leading to increased apoptosis in cancer cells.
Conclusions:
- miR-16 acts as a tumor suppressor by inhibiting FEAT translation.
- These findings elucidate a novel regulatory pathway involving miR-16 and FEAT in cancer progression.
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