长链非编码 RNA HOTAIR 通过海绵吸附 miR-331-3p 增强 RCC2 加速宫颈癌进展。
LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p.
机构信息
State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Department of Gynecologic Oncology Radiation Therapy (Ward II), Xinjiang Medical University, Xinjiang Medical University Third Clinical Medical College (Affiliated Tumor Hospital), Urumqi, 830011, Xinjiang, China.
Department of Internal Neurology, Xinjiang Uygur Autonomous Region Children's Hospital, Urumqi, 830000, Xinjiang, China.
出版信息
Clin Transl Oncol. 2023 Jun;25(6):1650-1660. doi: 10.1007/s12094-022-03059-4. Epub 2023 Jan 2.
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.
目的
长链非编码 RNA（lncRNA）已逐渐被视为各种癌症的重要指标。本研究旨在探讨 lncRNA HOTAIR 对宫颈癌进展的影响。
方法
采用 RT-qPCR 和 Western blot 检测 RNA 和蛋白表达。采用荧光原位杂交（FISH）检测 HOTAIR 的细胞内定位。通过 CCK-8、集落形成、Transwell 和划痕愈合实验检测癌细胞活力和迁移能力。通过荧光素酶报告实验验证 miR-331-3p 与 HOTAIR/RCC2 之间的结合关系。
结果
RT-qPCR 实验表明，HOTAIR 在宫颈癌组织和细胞系中明显上调。此外，荧光原位杂交（FISH）实验表明，HOTAIR 主要位于癌细胞的细胞质中，提示其具有海绵吸附功能。CCK-8、集落形成、Transwell 和划痕愈合实验表明，在 HeLa 和 SiHa 细胞中敲低 HOTAIR 可显著降低细胞生长、迁移和侵袭。随后，miR-331-3p 被证实是 HOTAIR 的靶分子。此外，Pearson 相关性分析结果表明，宫颈癌组织中 HOTAIR 与 miR-331-3p 呈负相关。HOTAIR 负调控 miR-331-3p 表达。最终，验证了 miR-331-3p 的靶基因是 RCC2，且 miR-331-3p 负调控 RCC2 表达。此外，对临床宫颈癌组织的分析证实了 miR-331-3p 与 RCC2 呈负相关。HOTAIR 和 RCC2 在 HeLa 和 SiHa 细胞中发挥致癌作用，而 miR-331-3p 则发挥相反的作用。
结论
HOTAIR 通过靶向 miR-331-3p/RCC2 轴在宫颈癌中发挥致癌作用。此外，临床宫颈癌组织证实了 miR-331-3p 与 lncRNA HOTAIR 和 RCC2 呈负相关。这些数据为宫颈癌提供了潜在的治疗靶点。
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