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Describing a Transcription Factor Dependent Regulation of the MicroRNA Transcriptome
Published on: June 15, 2016
Long Noncoding RNA ST7-AS1 Upregulates TRPM7 Expression by Sponging microRNA-543 to Promote Cervical Cancer
Hongguo Qi1, Lianwei Lu2, Lili Wang3
1Department of Gynaecology and Obstetrics, The Second Children & Women's Healthcare of Jinan City, Jinan, Shandong 250022, People's Republic of China.
Purpose:
ST7 antisense RNA 1 (ST7-AS1) is a long noncoding RNA that affects the progression of gastric cancer and laryngeal squamous cell carcinoma. Herein, ST7-AS1 expression was detected in cervical cancer tissues and cell lines. In addition, its biological roles in inducing the aggressive phenotype of cervical cancer and its associated mechanisms of action were illustrated.
Patients And Methods:
ST7-AS1 expression in cervical cancer tissues and cell lines was detected using quantitative real-time polymerase chain reaction (qRT-PCR). Malignancy was determined using Cell Counting Kit-8 assay, flow cytometry, transwell migration and invasion assays, and xenograft experiments. Bioinformatics analysis was performed to predict the interaction between ST7-AS1 and microRNA-543 (miR-543). Luciferase reporter assay, RNA immunoprecipitation assay, Western blotting, qRT-PCR, and rescue experiments were performed to further identify the interactions among ST7-AS1, miR-543, and transient receptor potential melastatin 7 (TRPM7).
Results:
ST7-AS1 was upregulated in cervical cancer tissues and cell lines. ST7-AS1 overexpression was correlated with a high International Federation of Gynecology and Obstetrics stage, frequent lymph node metastasis, deep cervical invasion, and short overall survival in patients with cervical cancer. ST7-AS1 inhibition hindered cervical cancer cell proliferation, migration, and invasion; ST7-AS1 downregulation resulted in marked cell apoptosis. Additionally, ST7-AS1 deficiency restricted cervical tumor growth in vivo. Mechanistically, ST7-AS1 functioned as competing endogenous RNA to increase TRPM7 expression by sponging miR-543. Intriguingly, rescue experiments revealed that miR-543 downregulation or TRPM7 overexpression abrogated the inhibitory actions of ST7-AS1 knockdown in the aggressive phenotype of cervical cancer cells.
Conclusion:
The newly identified ST7-AS1/miR-543/TRPM7 axis promoted the oncogenicity of cervical cancer cells both in vitro and in vivo. Our study highlighted the importance of this novel axis in cervical cancer progression, suggesting that this pathway can serve as a promising therapeutic target for cervical cancer.
Insights
The long noncoding RNA ST7 antisense RNA 1 (ST7-AS1) promotes cervical cancer progression by upregulating TRPM7 via sponging miR-543. Targeting this ST7-AS1/miR-543/TRPM7 axis offers a potential therapeutic strategy for cervical cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) play critical roles in various cancers.
- ST7 antisense RNA 1 (ST7-AS1) has been implicated in gastric and laryngeal cancers.
- The role of ST7-AS1 in cervical cancer remains largely unexplored.
Purpose of the Study:
- To investigate the expression and function of ST7-AS1 in cervical cancer.
- To elucidate the underlying molecular mechanisms of ST7-AS1 in promoting cervical cancer progression.
- To evaluate the therapeutic potential of targeting the ST7-AS1 pathway.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for ST7-AS1 expression analysis.
- Cell proliferation, apoptosis, migration, and invasion assays to assess cellular malignancy.
- Bioinformatics, luciferase reporter, and RNA immunoprecipitation assays to identify molecular interactions.
- Xenograft experiments for in vivo tumor growth evaluation.
Main Results:
- ST7-AS1 was significantly upregulated in cervical cancer tissues and cell lines.
- ST7-AS1 overexpression correlated with advanced disease stage, lymph node metastasis, and poor survival.
- ST7-AS1 promoted proliferation, migration, and invasion while inhibiting apoptosis; it also enhanced tumor growth in vivo.
- ST7-AS1 acted as a competing endogenous RNA (ceRNA) by sponging miR-543 to upregulate transient receptor potential melastatin 7 (TRPM7) expression.
Conclusions:
- The ST7-AS1/miR-543/TRPM7 axis is a novel pathway driving cervical cancer oncogenicity.
- ST7-AS1 inhibition effectively suppressed cervical cancer progression both in vitro and in vivo.
- This axis represents a promising therapeutic target for cervical cancer treatment.
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