RPL34-AS1-induced RPL34 inhibits cervical cancer cell tumorigenesis via the MDM2-P53 pathway

Cancer Sci. 2021 May;112(5):1811-1821. doi: 10.1111/cas.14874. Epub 2021 Mar 18.

Abstract

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.

Keywords: MDM2; P53; RPL34-AS1; cervical cancer; ribosomal protein L34.

MeSH terms

  • Adult
  • Animals
  • Carcinoma in Situ / etiology*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma in Situ / prevention & control
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • DEAD-box RNA Helicases / metabolism
  • Down-Regulation
  • Eukaryotic Initiation Factor-4A / metabolism
  • Female
  • HeLa Cells
  • Humans
  • Immunoprecipitation / methods
  • Mice
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins c-mdm2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • RNA, Long Noncoding / metabolism
  • Ribosomal Proteins / metabolism*
  • Tumor Suppressor Protein p53 / metabolism*
  • Uterine Cervical Neoplasms / etiology*
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / prevention & control

Substances

  • Neoplasm Proteins
  • RNA, Long Noncoding
  • Ribosomal Proteins
  • Tumor Suppressor Protein p53
  • ribosomal protein L34
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Eukaryotic Initiation Factor-4A
  • EIF4A3 protein, human
  • DEAD-box RNA Helicases