RNA adenosine modifications related to prognosis and immune infiltration in osteosarcoma

被引：39

作者：

Chen, Shijie ^{[1
,3
,4
]}

Zeng, Jin ^{[1
]}

Huang, Liping ^{[1
]}

Peng, Yi ^{[1
]}

Yan, Zuyun

Zhang, Aiqian ^{[2
]}

Zhao, Xingping ^{[2
]}

Li, Jun ^{[7
]}

Zhou, Ziting ^{[10
]}

Wang, Sidan ^{[10
]}

Jing, Shengyu ^{[10
]}

Hu, Minghua ^{[6
]}

Li, Yuezhan ^{[1
]}

Wang, Dong ^{[1
]}

Wang, Weiguo ^{[1
]}

Yu, Haiyang ^{[9
]}

Miao, Jinglei ^{[1
]}

Li, Jinsong ^{[1
]}

Deng, Youwen ^{[1
]}

Li, Yusheng ^{[8
]}

Liu, Tang ^{[5
]}

Xu, Dabao ^{[2
]}

机构：

[1] Cent South Univ, Dept Spine Surg, Xiangya Hosp 3, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China

[2] Cent South Univ, Dept Obstet & Gynecol, Xiangya Hosp 3, 138 Tongzipo Rd, Changsha 410013, Peoples R China

[3] East China Normal Univ, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[4] East China Normal Univ, Sch Life Sci, 500 Dongchuan Rd, Shanghai 200241, Peoples R China

[5] Cent South Univ, Xiangya Hosp 2, Dept Orthopaed, 139 Renmin Middle Rd, Changsha 410011, Hunan, Peoples R China

[6] Changsha Med Univ, Dept Anat Histol & Embryol, 1501 Leifeng Ave, Changsha 410219, Hunan, Peoples R China

[7] Anhui Med Univ, Dept Orthoped, Affiliated Hosp 2, 678 Furong Rd, Hefei 230601, Anhui, Peoples R China

[8] Cent South Univ, Xiangya Hosp, Dept Orthopead, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China

[9] Cent South Univ, Sch Basic Med Sci, 172 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China

[10] Cent South Univ, Xiangya Hosp 3, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China

来源：

JOURNAL OF TRANSLATIONAL MEDICINE | 2022年 / 20卷 / 01期

基金：

中国国家自然科学基金;

关键词：

RNA adenosine modifications; Osteosarcoma; Immune; Prognosis; Drugs; CANCER GROWTH; RESVERATROL; METASTASIS; INHIBITION; MICROENVIRONMENT; IDENTIFICATION; PROLIFERATION; METHYLATION; PROGRESSION; LANDSCAPE;

D O I：

10.1186/s12967-022-03415-6

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background RNA adenosine modifications, which are primarily mediated by "writer" enzymes (RMWs), play a key role in epigenetic regulation in various biological processes, including tumorigenesis. However, the expression and prognostic role of these genes in osteosarcoma (OS) remain unclear. Methods Univariate and multivariate Cox analyses were used to construct the RMW signature for OS using Target datasets. RMW expression in OS tissue was detected by qPCR analysis. Xcell and GSVA were used to determine the relationship between RMWs and immune infiltration. The DGIdb and CMap databases were used for drug prediction. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS. Results A 3-RMW (CSTF2, ADAR and WTAP) prognostic signature in OS was constructed using the Target dataset and verified using GEO datasets and 63 independent OS tissues via qPCR analysis. High-risk OS patients had poor overall survival, and the prognostic signature was an independent prognostic factor for OS. Functional studies showed that tumour-, metabolism-, cell cycle- and immune-related pathways were related to high risk. Next, we found that RMW-derived high-risk patients exhibited increased infiltration of M2 macrophages and cDCs. Furthermore, we predicted the potential drugs for OS using the DGIdb and CMap databases. In vivo and in vitro experiments showed that strophanthidin elicited antitumor activity against OS by repressing cell growth and inducing cell cycle arrest at the G1 phase. Conclusion The 3-RWM-based prognostic signature established in this study is a novel gene signature associated with immune infiltration, and strophanthidin was identified as a candidate therapy for OS by repressing OS cell growth and the cell cycle.

引用

页数：17

共 58 条

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