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Ring finger protein 38 promote non-small cell lung cancer progression by endowing
cell EMT phenotype
#MMPMID29581762
Xiong D
; Zhu SQ
; Wu YB
; Jin C
; Jiang JH
; Liao YF
; Long X
; Wu HB
; Xu JJ
; Li JJ
; Ding JY
J Cancer
2018[]; 9
(5
): 841-850
PMID29581762
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Objectives: Ring finger protein 38 (RNF38), as an E3 ubiquitin ligase, plays an
essential role in multiple biological processes by controlling cell apoptosis,
cell cycle and DNA repair, and resides in chromosome 9 (9p13) which is
involvement in cancer pathogenesis including lung cancer. However, its function
in tumorigenesis remains unclear. Hence, this study set out to investigate the
biological function and clinical implications of RNF38 in non-small cell lung
cancer (NSCLC). Materials and Methods: Immunohistochemistry, quantitative
real-time polymerase chain reaction (qRT-PCR) and western blot were used to
detect RNF38 protein and mRNA levels in NSCLC and corresponding paratumor
tissues. Tissue microarrays (TMA) analysis of 208 NSCLC cases were used to
evaluate the relationship between RNF38 expression and clinical implications.
Prognostic value was assessed by Kaplan-Meier analysis and log-rank tests.
Wound-healing assays, trans-well assays, colony formation assays and CCK8 were
used to assess cell migration, invasion and proliferative ability respectively.
The analysis of epithelial-to-mesenchymal transition (EMT) phenotype was carried
out by immunofluorescence and western blot. Results: Our data revealed that
elevated RNF38 expression were more common in NSCLC tissues than paired normal
tissues in both mRNA (2.82 ± 0.29 vs. 1.23 ± 0.13) and protein (2.75 ± 0.09 vs.
1.24 ± 0.02) level. High levels of RNF38 expression were significantly associated
with lymph node metastases, higher TNM stages (p=0.011), larger tumor size
(p=2.09E-04) and predicted poor prognosis. RNF38 expression was inversely
correlated with E-cadherin expression (P= 0.025). Moreover, downregulation of
RNF38 impaired the proliferation, metastatic and invasive abilities in NSCLC
cells. In addition, aberrant RNF38 expression could modulate the key molecules of
EMT. Conclusions: Our results indicate that elevated expression of RNF38 is
significantly associated with the proliferation and metastatic capacity of NSCLC
cells, and RNF38 overexpression can serve as a biomarker of NSCLC poor prognosis.
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