4.5 Article

NOP2/Sun RNA methyltransferase 2 promotes tumor progression via its interacting partner RPL6 in gallbladder carcinoma

Journal

CANCER SCIENCE
Volume 110, Issue 11, Pages 3510-3519

Publisher

WILEY
DOI: 10.1111/cas.14190

Keywords

gallbladder carcinoma; NOP2; Sun domain family member 2; ribosomal protein L6; translational regulation; tumor progression

Categories

Funding

  1. China Postdoctoral Science Foundation [2017M61025] Funding Source: Medline
  2. National Natural Science Foundation of China [31620103910, 31701124, 81874181, 91440203] Funding Source: Medline
  3. General Surgery Construction Program of Shanghai Municipal Health Commission [2017ZZ02011] Funding Source: Medline
  4. Postdoctoral Initial Foundation of Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine [2018BSH02] Funding Source: Medline
  5. Emerging Frontier Program of Hospital Development Center [SHDC12018107] Funding Source: Medline
  6. Shanghai Science and Technology Committee Rising-Star Program [19QA14 05900] Funding Source: Medline
  7. Shanghai Key Laboratory of Biliary Tract Disease Research Foundation [17DZ2260200] Funding Source: Medline

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NOP2/Sun domain family, member 2 (NSUN2) is a nuclear RNA methyl-transferase catalyzing 5-methylcytosine formation. Evidence shows that NSUN2 is correlated with cell unlimited proliferation. However, its functional role in gallbladder carcinoma (GBC), which is the most common biliary tract malignancy and has a poor prognosis, remains to be determined. Here we found that NSUN2 was highly expressed in GBC tissues as well as cell lines. NSUN2 silencing repressed GBC cell proliferation and tumorigenesis both in vitro and in vivo. Conversely, upregulation of NSUN2 enhanced GBC cell growth and colony formation. We further discovered that RPL6 was a closely interacting partner with NSUN2. Silencing RPL6 resulted in insufficient NSUN2 translational level and accumulative NSUN2 transcriptional level. Exogenous expression of NSUN2 partially rescued the effect of RPL6 in gallbladder cancer progression. Taken together, our data provided novel mechanic insights into the function of NSUN2 in GBC, thus pointing to NSUN2 as a potential and effective therapeutic approach to GBC treatment.

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