J Cancer 2021; 12(20):6031-6049. doi:10.7150/jca.60748 This issue

Research Paper

SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis

Sun Gui Feng1,2, Rajeev Bhandari1, Liu Ya2, Bian Zhixuan3, Pan Qiuhui3, Zhu Jiabei3, Mao sewi3, Zhen Ni3, Wang Jing3, Sun Fenyong2, Ma Ji3✉, Ramesh Bhandari2✉

1. Department of Clinical Laboratory Medicine, Chengdu Second Peoples Hospital, Chengdu, Sichuan 610021, PR China.
2. Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital, Tongji University of Medicine Shanghai, China.
3. Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, China.

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Citation:
Feng SG, Bhandari R, Ya L, Zhixuan B, Qiuhui P, Jiabei Z, sewi M, Ni Z, Jing W, Fenyong S, Ji M, Bhandari R. SNHG9 promotes Hepatoblastoma Tumorigenesis via miR-23a-5p/Wnt3a Axis. J Cancer 2021; 12(20):6031-6049. doi:10.7150/jca.60748. Available from https://www.jcancer.org/v12p6031.htm

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Abstract

Graphic abstract

Background: Hepatoblastoma is a common hepatic tumor occurring in children between 0-5 years. Accumulating studies have shown lncRNA's potential role in distinct cancer progression and development, including hepatoblastoma. SnoRNA host gene 9 (SNHG9) is associated with the progression of distinct human cancers, but, its specific molecular mechanisms in hepatoblastoma is not unknown.

Methods: In this study, we estimated SNHG9 expression in hepatoblastoma tissue and cell lines by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Next, we downregulated and upregulated SNHG9 expression in hepatoblastoma cell lines and then determined cell proliferation (CCK-8), colony formation, and cellular apoptosis activity. The dual luciferase reporter activity, RNA immunoprecipitation (RIP), biotin RNA pull down and Spemann's Pearson correlation coefficient assay were performed to establish the interaction between SNHG9, WNt3a and miR- 23a-5p. A xenograft in-vivo tumorgenicity test was performed to elucidate the role of SNHG9 hepatoblastoma in tumorigenesis. SNHG9 role in Cisplatin drug resistance in hepatoblastoma was also determined.

Results: SNHG9 was significantly upregulated in hepatoblastoma tissue and cell lines. SNHG9 overexpression on HUH6 & HepG2 resulted in a significant increase in cell proliferation and clonogenic activity while SNHG9 knock down resulted in a sustained inhibition of cell proliferation and clonogenic activity. Dual luciferase activity, RNA immunoprecipitation and biotin pull down confirmed the direct interaction of miR-23a-5p with SNHG9. The xenograft tumorgenicity test showed SNHG9 downregulation significantly inhibited the tumor growth in BALB/c mice. ROC and Kaplan-Meier analysis showed potential prognostic and diagnostic importance of SNHG9 in hepatoblastoma.

Conclusion: We concluded that SNHG9/miR-23a-5p/Wnt3a axis promotes the progression hepatoblastoma tumor.

Keywords: Hepatoblastoma, LncRNA, miRNA, miR-23a-5p, SNHG9