Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 DOI: 10.1159/000488265 © 2018 The Author(s) www.karger.com/cpb online:March March19,19, 2018 Published online: 2018 Published by S. Karger AG, Basel and Biochemistry Published www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer Accepted: December 09, 2017
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Original Paper
C/D-Box Snord105b Promotes Tumorigenesis in Gastric Cancer via ALDOA/C-Myc Pathway Cong Zhang Lian-mei Zhao Bao-en Shan
Hao Wu
Guo Tian
Su-li Dai
Ri-yang Zhao
Research Centre, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China
Key Words Small nucleolar RNA • Snord105b • Gastric cancer • Carcinogenesis Abstract Background/Aims: Small nucleolar RNAs (snoRNAs) play an important role in carcinogenesis. ,QWKLVVWXG\ZHLGHQWLÀHGD&'ER[VQR51$VQRUGEDQGIXUWKHULQYHVWLJDWHGWKHIXQFWLRQ and mechanism of the snord105b in gastric cancer (GC). Methods: 7KH H[SUHVVLRQ OHYHO RI VQRUGE LQ *& WLVVXUHV VHUD DQG FHOO OLQHV ZHUH GHWHFWHG E\ T573&5 &HOO YLDELOLW\ ZDV assessed using MTS assay. Transwell and wound healing assay were performed to evaluate PLJUDWLRQ DQG LQYDVLRQ DQG SURWHLQ H[SUHVVLRQ ZDV H[DPLQHG E\ ZHVWHUQ EORWWLQJ &K,53 and MS analysis was used to seek for the special binding protein of snord105b. Results: The snord105b was upregulated and associated with tumor size, differentiation, and pathological stage in GC. Snord105b affected proliferation, migration and invasion in multiple GC cell lines. 7KH RQFRJHQLF DFWLYLW\ RI VQRUGE ZDV DOVR FRQÀUPHG ZLWK in vivo data. Mechanistically, VQRUGE VSHFLÀFDOO\ ERXQG WR $/'2$ DQG DIIHFWHG &P\F ZKLFK SOD\V D NH\ UROH LQ carcinogenesis and tumor development. Conclusion: Snord105b appears to be a novel oncogene and is clinically and functionally involved in the development of GC. Targeting snord105b and its pathway may provide new biomarkers or potential treatments for patients with GC. © 2018 The Author(s) Published by S. Karger AG, Basel
Introduction
GC is one of the most common cancers and is the third highest cause of cancer-related Ǥ
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Baoen Shan
Research Centre, the Fourth Hospital of Hebei Medical University, 12# Jiankang road, Shijiazhuang (China) Tel. +86311-86095283, E-Mail
[email protected]
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs (ncRNAs) that are
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Ǥ Materials and Methods Patients and healthy donors Fresh GC tissues and adjacent normal gastric tissues in patients with GC were collected from the Fourth
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Cells culture and transfection
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RNA isolation and quantitative real-time PCR (q-PCR)
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Transwell migration and invasion assay ǡ ͳ έ ͳͲͷ ǦͻͲͳ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
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ʹͶͶͺǤ experiments were performed in triplicate.
Clonogenic assay
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Animal experiments Ȁ
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Results
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Fig. 1.ͳͲͷ ǡ
ǤȋȌͳͲͷ
ǦȋαͳͲͻǡȗδͲǤͲͷȌǤͳͲͷ Ǥ ȋȌ ͳͲͷ
Ǥ ȋȌ ͳͲͷ Ȃ
ȋ α ͺǡ ȗδͲǤͲͷȌǤȋǦȌǦǦͳͲͷ
ǦͳǤ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
ȋ α ͳͲͻȌǤ Ǥ ͳ Table 1.
ͳͲͷ Ǥͳǡ
ͳͲͷ
ǡɖʹǦǤȗ ϐ
ϐ
compared with the corresponding normal Expression level of snord105b Parameters Total P-value Low High
ȋ δ Age/year ͲǤͲͷȌǤ ǡ 5 43 5 38 ͳͲͷ Differentiation 49 16 33 0.015* ȋαͺȌǦǤ Well Poor 60 8 52 Ǥͳǡ
ͳͲͷ Stage 21 8 13 0.014* ϐ
ĉ-Ċ 88 11 77 ċ
Cancer thrombus yes 52 8 44 0.162 ȋα͵ͲǡδͲǤͲͷȌǤ no 57 15 42 ͳͲͷ
ǦͺͲ͵ǡ Ǧͺʹ͵ǡ ǦͻͲͳǡ ǦʹǤ Ǧ ͳǡ ͳͲͷ
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ȋ Ǥ ͳ ͳȌǤ
ͳͲͷ characteristic of GC.
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in vitro
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in vivo.
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Fig. 2. ͳͲͷ ǡ ǡ
Ǥ ȋȌ ͳͲͷ
Ǧ ǦͻͲͳ
ʹͶ ǡ ȗδͲǤͲͷǤ ȋȌ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Fig. 3.
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ȋ α ȌǤ ȋ Ȍ ȋ Ȍ ǤȋǦ ȌͳͲͷ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Fig. 4. ͳͲͷ
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Fig. 5.ͳͲͷ in the nucleus and promote tumoriȀǦ
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ͳͲͷ Ǥ ȋǦȌ ǡ Ǧ
ʹ ǦͻͲͳ
Ͷͺ Ǥ ȋȌ of nude mice. (E-F) Representa
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the two groups of nude mice.
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ͳͲͷ Ǥ
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pathway ȋ Ȍ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
Fig. 6. ͳͲͷ functioned through its association with Ǥ ȋȌ
Ȃ cells transfected pression plasmid ʹͶ ǡ ȗδͲǤͲͷǤ ȋȌ
GC cells transfected pression plasmid ʹͶ Ǥ ȋȌ
Ȃ in GC cells transfected with the ͳͲͷ ͳͲͷ ʹͶ ǡ ȗδͲǤͲͷǤ ȋȌ GC cells with snorͳͲͷ
expression was as ǡ ȗδͲǤͲͷǤ
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sion on the migration (E and F) and ȋ Ȍ
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ϐǡȗδͲǤͲͷǤȋ ȌǦ
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ȀǦ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
ͷͶͻ
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ǦͻͲͳ ȋ Ǥ ȌǤ
ϐ Ǧ ȋ Ǥ ȌǤ ǡ ͳͲͷ
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ͳͲͷǦ
Ǧȋ ǤȌǤǡ
ͳͲͷ
ͳͲͷȀ
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ǤǤ Discussion
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ȏͳͳǦͳ͵ȐǤǡ
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ǡ Ǥ
ͳͲͷ
ǡ ǡ
ǡ ͳͲͷ
ǡ Ǥ
ͳͲͷ of GC. ǡ
Ǧ ǡ
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ȏʹʹǦʹȐǤǤ
ȏʹȐǤ ǤǦ
metastasis of pancreatic cancer cellsȏͳͲȐǤ ǡ
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Ǥ ǡ ͳͲͷ ϐ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
ȀǦ
ǡͳͲͷ
target for GC. Acknowledgements
ȋ Ǥ ͺͳ͵ͳͶʹǡ ͺͳͷͲʹͲ͵ʹǡ ͺͳʹͷͷͲȌǡ
ȋ ͲǤʹͲͳͷʹͲ͵ȌǤ ǤǤǤ
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Ǥ Disclosure Statement
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Ǥ References ͳ ʹ ͵ Ͷ
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Physiol Biochem 2018;45:2471-2482 Cellular Physiology Cell © 2018 The Author(s). Published by S. Karger AG, Basel DOI: 10.1159/000488265 and Biochemistry Published online: March 19, 2018 www.karger.com/cpb Zhang et al.: Snord105b Promotes Tumorigenesis in Gastric Cancer
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