Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
Department of pathology, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, P.R. China.
Cancer Sci. 2021 May;112(5):1811-1821. doi: 10.1111/cas.14874. Epub 2021 Mar 18.
Ribosomal proteins (RPs) are important components of ribosomes and related to the occurrence and development of tumors. However, little is known about the effects of the RP network on cervical cancer (CC). In this study, we screened differentially expressed RPL34 in CC by high-throughput quantitative proteome assay. We found that RPL34 acted as a tumor suppressor and was downregulated in CC and inhibited the proliferation, migration, and invasion abilities of CC cells. Next, we verified that RPL34 regulated the CC through the MDM2-P53 pathway by using Act D medicine, MDM2 inhibitor, and a series of western blotting（WB）assays. Moreover, an antisense lncRNA, RPL34-AS1, regulated the expression of RPL34 and participated in the tumorigenesis of CC. RPL34 can reverse the effect of RPL34-AS1 in CC cells. Finally, by RNA-binding protein immunoprecipitation (RIP) assay we found that eukaryotic initiation factor 4A3 (EIF4A3), which binds to RPL34-AS1, regulated RPL34-AS1 expression in CC. Therefore, our findings indicate that RPL34-AS1-induced RPL34 inhibits CC cell proliferation, invasion, and metastasis through modulation of the MDM2-P53 signaling pathway, which provides a meaningful target for the early diagnosis and treatment of CC.
核糖体蛋白（RPs）是核糖体的重要组成部分，与肿瘤的发生和发展有关。然而，关于核糖体蛋白网络对宫颈癌（CC）的影响知之甚少。在这项研究中，我们通过高通量定量蛋白质组学检测筛选出 CC 中差异表达的 RPL34。我们发现 RPL34 作为一种肿瘤抑制因子在 CC 中下调，并抑制 CC 细胞的增殖、迁移和侵袭能力。接下来，我们通过使用 Act D 药物、MDM2 抑制剂和一系列 Western blot（WB）检测，验证了 RPL34 通过 MDM2-P53 通路调节 CC。此外，反义长链非编码 RNA RPL34-AS1 调节 RPL34 的表达并参与 CC 的肿瘤发生。RPL34 可以逆转 RPL34-AS1 在 CC 细胞中的作用。最后，通过 RNA 结合蛋白免疫沉淀（RIP）检测，我们发现与 RPL34-AS1 结合的真核起始因子 4A3（EIF4A3）调节 CC 中 RPL34-AS1 的表达。因此，我们的研究结果表明，RPL34-AS1 诱导的 RPL34 通过调节 MDM2-P53 信号通路抑制 CC 细胞的增殖、侵袭和转移，为 CC 的早期诊断和治疗提供了有意义的靶点。
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