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Authors Liu Q, Li Y, Lv W, Zhang G, Tian X, Li X, Cheng H, Zhu C
Received 18 December 2017
Accepted for publication 21 February 2018
Published 1 May 2018 Volume 2018:11 Pages 2475—2487
DOI https://doi.org/10.2147/OTT.S160192
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Tohru Yamada
Background: Renal cell carcinoma (RCC) is the most common cancer in kidney
malignancies. UCA1 has been identified as an oncogenic lncRNA in multiple
cancers, including RCC. However, the underlying molecular mechanism of UCA1
involved in RCC progression is far from being addressed.
Methods: Reverse-transcription quantitative polymerase chain reaction
(RT-qPCR) assays were used to measure expressions of UCA1, miR129, and SOX4
mRNA. Western blot assays were employed to detect SOX4 protein expression. Cell
proliferation, invasion, and apoptosis were assessed by CCK-8, Matrigel
invasion, and annexin–fluorescein isothiocyanate (FITC) apoptosis-detection
assays, respectively. The interaction between UCA1 and miR129 was demonstrated
by luciferase, RNA pull-down, and RNA-immunoprecipitation (RIP) assays.
Luciferase assays were also used to explore whether UCA1 was able to act as a
molecular sponge of miR129 to affect the interplay of miR129 and SOX4.
Results: UCA1 expression was upregulated in RCC tissue and cells, and
higher UCA1 expression was associated with advanced pathogenic status and poor
prognosis of RCC patients. UCA1 knockdown suppressed proliferation and invasion
and induced apoptosis in RCC cells. UCA1 inhibited miR129 expression by direct
interaction in RCC cells. miR129 overexpression inhibited cell proliferation
and invasion and promoted apoptosis. Moreover, miR129 downregulation abrogated
UCA1 knockdown-mediated antiproliferation, anti-invasion, and proapoptosis
effects in RCC cells. Furthermore, UCA1 acted as a ceRNA of miR129 to enhance
target-gene SOX4 expression in RCC cells.
Conclusion: UCA1 promoted cell proliferation and invasion and inhibited
apoptosis by regulating SOX4 via miR129 in RCC, offering a promising
therapeutic target and prognosis marker for RCC patients.
Keywords: renal cell carcinoma, lncRNA, UCA1, miR129, SOX4, UCA1/miR129/SOX4
axis