Abstract
Purpose
Long noncoding RNAs (lncRNAs) have been gradually regarded as influential indicators of various cancers. The present study aimed to identify the effects of lncRNA HOTAIR on cervical cancer progression.
Methods
RNA and protein expressions were quantified by RT-qPCR and western blot assays. Fluorescence in situ hybridization (FISH) assay was carried out to examine the intracellular location of HOTAIR. Cancer cell viability and mobility were detected by CCK-8, colony formation, transwell and wound healing assays. Binding relationships between miR-331-3p and HOTAIR/RCC2 were validated by luciferase reporter assay.
Results
RT-qPCR assays showed that HOTAIR levels were notably upregulated in cervical cancer tissues and cell lines. Furthermore, a fluorescence in situ hybridization (FISH) assay suggested that HOTAIR was mostly located in the cytoplasm of cancer cells, indicating a sponging function. CCK-8, colony formation, Transwell and wound-healing assays indicated that knockdown of HOTAIR in HeLa and SiHa cells significantly reduced cell growth, migration and invasion. Subsequently, miR-331-3p was proven to be the target molecule of HOTAIR. In addition, results from Pearson's correlation analysis indicated negative correlation between HOTAIR and miR-331-3p in cervical cancer tissues. HOTAIR negatively modulated miR-331-3p expression. Ultimately, the target gene of miR-331-3p was verified to be RCC2, and miR-331-3p negatively modulated RCC2 expression. In addition, analysis on clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p and RCC2. HOTAIR and RCC2 showed oncogenic functions in HeLa and SiHa cells, while miR-331-3p exerted the reverse effect.
Conclusions
HOTAIR plays a carcinogenic role in cervical cancer by targeting the miR-331-3p/RCC2 axis. Moreover, clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p with lncRNA HOTAIR and RCC2. These data suggested an underlying therapeutic target for cervical cancer.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
We gratefully acknowledge the financial support from the State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia Fund. At the same time, we would like to thank all the researchers and study participants for their contributions.
Funding
This study was supported by grants from the State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia Fund (Grant number: SKL-HIDCA-2019–31).
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GB and GA are responsible for the conception or design of the work. GB, AA, XL and GA contributed to the acquisition, analysis, and interpretation of the data for the work. AA and XL provided the tissue samples. AA helped in the follow-up of the patients. XL helped in reviewing the histopathology slides. GB is the guarantor of the article. All authors approved the final manuscript version to be published.
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The study was approved by Ethical Committee of Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital) and conducted in accordance with the ethical standards.
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Buranjiang, G., Abuduwanke, A., Li, X. et al. LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p. Clin Transl Oncol 25, 1650–1660 (2023). https://doi.org/10.1007/s12094-022-03059-4
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DOI: https://doi.org/10.1007/s12094-022-03059-4