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Published on: March 30, 2019
LncRNA PCBP1-AS1 suppresses cell growth in oral squamous cell carcinoma by targeting miR-34c-5p/ZFP36 axis
Orkideh Shafiee Allaf1, Wenhao Li2, Chongmai Zeng3
1Department of Orthodontics, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong, 510055, China. orkideh@163.com.
Abstract:
Oral squamous cell carcinoma (OSCC) is the most frequently diagnosed oral malignancy and poses a great threat to public health. According to bioinformatics analysis, long noncoding RNA PCBP1-AS1 is downregulated in OSCC. In this work, the functions and mechanism of PCBP1-AS1 in OSCC were further investigated. PCBP1-AS1 expression in OSCC cells was measured by quantitative polymerase chain reaction. Cell viability and proliferation were detected using CCK-8 assays and colony-forming assays. TUNEL assays as well as flow cytometry analyses were carried out to detect OSCC cell apoptosis. Binding relationship between PCBP1-AS1 and miR-34c-5p or that between miR-34c-5p and ZFP36 in OSCC cells was identified using RNA immunoprecipitation assays, RNA pulldown assays, and luciferase reporter assays. Experimental results revealed that PCBP1-AS1 was downregulated in OSCC cells. PCBP1-AS1 overexpression hampered cell proliferation and enhanced cell apoptosis in OSCC. PCBP1-AS1 interacted with miR-34c-5p in OSCC and negatively regulated miR-34c-5p. ZFP36 3'untranslated region was targeted by miR-34c-5p. PCBP1-AS1 positively regulated ZFP36 expression. ZFP36 silencing abrogated the suppressive impact of PCBP1-AS1 on OSCC cell growth. In summary, PCBP1-AS1 suppresses cell growth in OSCC by upregulating ZFP36 through interaction with miR-34c-5p.
Insights
Long noncoding RNA PCBP1-AS1 is downregulated in oral squamous cell carcinoma (OSCC). PCBP1-AS1 suppresses OSCC cell growth by upregulating ZFP36 via interaction with miR-34c-5p.
Area of Science:
- Molecular biology
- Oncology
- Genetics
Background:
- Oral squamous cell carcinoma (OSCC) is a prevalent and dangerous oral malignancy.
- Bioinformatics analysis indicates long noncoding RNA PCBP1-AS1 is downregulated in OSCC.
- Understanding the role of PCBP1-AS1 in OSCC is crucial for developing new therapeutic strategies.
Purpose of the Study:
- To investigate the functions and molecular mechanisms of PCBP1-AS1 in OSCC.
- To determine the expression levels of PCBP1-AS1 in OSCC cells.
- To elucidate the regulatory pathway involving PCBP1-AS1, miR-34c-5p, and ZFP36 in OSCC.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) for gene expression analysis.
- Cell viability, proliferation (CCK-8, colony-forming assays), and apoptosis (TUNEL, flow cytometry) assays.
- RNA immunoprecipitation (RIP), RNA pulldown, and luciferase reporter assays to identify molecular interactions.
Main Results:
- PCBP1-AS1 expression was found to be significantly downregulated in OSCC cells.
- Overexpression of PCBP1-AS1 inhibited OSCC cell proliferation and induced apoptosis.
- PCBP1-AS1 directly interacted with miR-34c-5p, negatively regulating its expression.
- miR-34c-5p targeted the 3'untranslated region of ZFP36.
- PCBP1-AS1 positively regulated ZFP36 expression, and ZFP36 silencing reversed the effects of PCBP1-AS1.
Conclusions:
- PCBP1-AS1 acts as a tumor suppressor in OSCC.
- PCBP1-AS1 inhibits OSCC cell growth by upregulating ZFP36 through the miR-34c-5p pathway.
- This regulatory axis presents a potential therapeutic target for OSCC treatment.
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