Abstract
Background: Small nucleolar RNA host gene 12 (SNHG12) is a newly identified long non-coding RNA (lncRNA) whose involvements have been explored in several cancers. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho.Methods: RT-PCR was performed to examine the expressions of SNHG12, miR-199a-5p and Klotho in ICC cells. Cell counting kit-8 (CCK-8), colony formation assays and transwell assays were applied to analyze the proliferation, migration and invasion of ICC cells. Luciferase assays, RIP assays and RNA pull-down assays were carried out to demonstrate the direct binding relationships among SNHG12, miR-199a-5p and Klotho. The xenograft nude models were applied to test the effects of SNHG12 on ICC tumor growth.Results: The expression of SNHG12 and Klotho was distinctly increased in ICC cells, while miR-199a-5p expressions were decreased. Functionally, the silence of SNHG12 inhibited the proliferation and metastasis of ICC cells, while miR-199a-5p overexpression exhibited an opposite result. Mechanistically, Knockdown of SNHG12 significantly suppressed the expressions of miR-199a-5p by sponging it, and then increased Klotho expression. The final in vivo experiments suggested that the silence of SNHG12 distinctly inhibited tumor growth.Conclusion: Our findings indicated that SNHG12 inhibited cell proliferation and metastasis process of ICC cells through modulating the miR-199a-5p/Klotho axis and it is expected to become a potential therapeutic target for ICC.
Highlights
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous group of malignancies that occur at any location along the biliary tree [1, 2]
To identify the functional long non-coding RNA (lncRNA) in ICC progression, we searched TCGA datasets and focused on Small nucleolar RNA host gene 12 (SNHG12) which was distinctly overexpressed in ICC specimens (n = 36) compared with non-tumor specimens (n = 9) (Figure 1A)
RTPCR assays showed that SNHG12 expression was distinctly increased in four ICC cell lines compared with BEC cells (Figure 1B)
Summary
Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous group of malignancies that occur at any location along the biliary tree [1, 2]. One of the most effective treatments remains surgical removal for ICC patients [4]. For these patients with advanced stages, operative treatments provide limited chances [5]. It is necessary to develop novel adjuvant therapies for the improved prognosis of ICC patients. The poor understanding of the mechanisms underlying the development and progression of ICC restricts the developments of novel approaches. It is necessary to establish molecular modulators influencing developments and progression of ICC, which will promote the developments of efficient therapies. Our study aimed to explore the functions of SNHG12 on intrahepatic cholangiocarcinoma (ICC) progression and its interaction with miR-199a-5p and Klotho
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