• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

长链非编码RNA KASRT通过调节骨肉瘤中与SRSF1相关的KLF6可变剪接和P21/CCND1通路作为潜在治疗靶点：一项……研究 （原文中“An and Study”表述不完整，可能存在信息缺失）

LncRNA KASRT Serves as a Potential Treatment Target by Regulating SRSF1-Related KLF6 Alternative Splicing and the P21/CCND1 Pathway in Osteosarcoma: An and Study.

作者信息

Chen Kai, Li Cheng, Huang Shuai, Chen Yu, Zhu Xiaodong

机构信息

Department of Orthopedics, Changhai Hospital, Second Military Medical University, Shanghai, China.

Department of Orthopedics, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Front Oncol. 2021 Sep 9;11:700963. doi: 10.3389/fonc.2021.700963. eCollection 2021.

DOI:10.3389/fonc.2021.700963
PMID:34568030
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8458968/
Abstract

PURPOSE

Long non-coding RNA KLF6 alternative splicing regulating transcript (lnc-KASRT) locates within the intronic region of SRSF1, possessing the potential to regulate KLF6 alternative splicing to promote carcinogenicity. Then, the current and study aimed to investigate the effect of lnc-KASRT on regulating tumor malignant behaviors, and the implication of its interaction with KLF6 alternative splicing in osteosarcoma.

METHODS

Lnc-KASRT overexpression or knockdown plasmid was transfected into U-2OS and Saos-2 cells. Then, KLF6-SV1 knockdown plasmid with or without lnc-KASRT overexpression plasmid was transfected into these cells for compensative experiments. , lnc-KASRT overexpression or knockdown Saos-2 cells were injected in mice for tumor xenograft construction.

RESULTS

Lnc-KASRT expression was increased in most osteosarcoma cell lines compared to control cell line. Lnc-KASRT overexpression promoted cell viability, mobility, and anti-apoptotic marker expression, while reducing apoptosis rate and pro-apoptotic marker expression; meanwhile, it regulated SRSF1, KLF6 alternative splicing (increased KLF6-splice variant 1 (KLF6-SV1), decreased KLF6-wild type (KLF6-WT)), and followed P21/CCND1 pathway in U-2OS/Saos-2 cells. The lnc-KASRT knockdown exhibited opposite trends. Subsequent compensative experiments disclosed that KLF6-SV1 knockdown attenuated most of the tumor-promoting effects of lnc-KASRT overexpression in U-2OS/Saos-2 cells. experiments further validated that lnc-KASRT enhanced tumor growth and reduced tumor apoptosis; meanwhile, it also increased tumor KLF6-SV1, MMP-1, and MMP-9 expressions but decreased tumor SRSF1 and KLF6-WT expressions in xenograft mice.

CONCLUSION

Lnc-KASRT serves as a potential treatment target regulating SRSF1-related KLF6 alternative splicing and following P21/CCND1 pathway in osteosarcoma.

摘要

目的

长链非编码RNA KLF6可变剪接调控转录本（lnc-KASRT）位于SRSF1的内含子区域，具有调控KLF6可变剪接以促进致癌作用的潜力。因此，本研究旨在探讨lnc-KASRT对肿瘤恶性行为的调控作用及其与KLF6可变剪接在骨肉瘤中的相互作用。

方法

将lnc-KASRT过表达或敲低质粒转染至U-2OS和Saos-2细胞中。然后，将带有或不带有lnc-KASRT过表达质粒的KLF6-SV1敲低质粒转染至这些细胞中进行补偿实验。此外，将lnc-KASRT过表达或敲低的Saos-2细胞注射到小鼠体内构建肿瘤异种移植模型。

结果

与对照细胞系相比，大多数骨肉瘤细胞系中lnc-KASRT表达增加。lnc-KASRT过表达促进细胞活力、迁移能力及抗凋亡标志物表达，同时降低凋亡率和促凋亡标志物表达；同时，它在U-2OS/Saos-2细胞中调控SRSF1、KLF6可变剪接（增加KLF6剪接变体1（KLF6-SV1），降低KLF6野生型（KLF6-WT）），并遵循P21/CCND1途径。lnc-KASRT敲低则表现出相反的趋势。随后的补偿实验表明，KLF6-SV1敲低减弱了lnc-KASRT过表达在U-2OS/Saos-2细胞中的大部分促肿瘤作用。体内实验进一步证实，lnc-KASRT促进肿瘤生长并减少肿瘤凋亡；同时，它还增加了异种移植小鼠肿瘤中KLF6-SV1、MMP-1和MMP-9的表达，但降低了肿瘤中SRSF1和KLF6-WT的表达。

结论

lnc-KASRT作为一个潜在的治疗靶点，在骨肉瘤中调控与SRSF1相关的KLF6可变剪接并遵循P21/CCND1途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/9b179425c7d2/fonc-11-700963-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/6f733ac62e89/fonc-11-700963-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/95493f4325c4/fonc-11-700963-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/13f1fda27b4f/fonc-11-700963-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/6e3725a326ff/fonc-11-700963-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/9d0d9ffef548/fonc-11-700963-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/11f75a310758/fonc-11-700963-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/27e40bb20eed/fonc-11-700963-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/516ac37628cc/fonc-11-700963-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/22302a12775d/fonc-11-700963-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/d8f4bcc5a898/fonc-11-700963-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/9b179425c7d2/fonc-11-700963-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/6f733ac62e89/fonc-11-700963-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/95493f4325c4/fonc-11-700963-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/13f1fda27b4f/fonc-11-700963-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/6e3725a326ff/fonc-11-700963-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/9d0d9ffef548/fonc-11-700963-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/11f75a310758/fonc-11-700963-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/27e40bb20eed/fonc-11-700963-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/516ac37628cc/fonc-11-700963-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/22302a12775d/fonc-11-700963-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/d8f4bcc5a898/fonc-11-700963-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8725/8458968/9b179425c7d2/fonc-11-700963-g011.jpg

相似文献

1
LncRNA KASRT Serves as a Potential Treatment Target by Regulating SRSF1-Related KLF6 Alternative Splicing and the P21/CCND1 Pathway in Osteosarcoma: An and Study.长链非编码RNA KASRT通过调节骨肉瘤中与SRSF1相关的KLF6可变剪接和P21/CCND1通路作为潜在治疗靶点：一项……研究 （原文中“An and Study”表述不完整，可能存在信息缺失）
Front Oncol. 2021 Sep 9;11:700963. doi: 10.3389/fonc.2021.700963. eCollection 2021.
2
Hepatocyte growth factor enhances alternative splicing of the Kruppel-like factor 6 (KLF6) tumor suppressor to promote growth through SRSF1.肝细胞生长因子增强 Kruppel 样因子 6（KLF6）肿瘤抑制因子的可变剪接，通过 SRSF1 促进生长。
Mol Cancer Res. 2012 Sep;10(9):1216-27. doi: 10.1158/1541-7786.MCR-12-0213. Epub 2012 Aug 2.
3
Effects of Kruppel-like factor 6 on osteosarcoma cell biological behavior.Kruppel样因子6对骨肉瘤细胞生物学行为的影响。
Tumour Biol. 2013 Apr;34(2):1097-105. doi: 10.1007/s13277-013-0651-0. Epub 2013 Jan 16.
4
Ras promotes growth by alternative splicing-mediated inactivation of the KLF6 tumor suppressor in hepatocellular carcinoma.在肝细胞癌中，Ras通过可变剪接介导的KLF6肿瘤抑制因子失活来促进生长。
Gastroenterology. 2008 May;134(5):1521-31. doi: 10.1053/j.gastro.2008.02.015. Epub 2008 Feb 13.
5
A small interfering RNA targeting the KLF6 splice variant, KLF6-SV1, as gene therapy for gastric cancer.针对 KLF6 剪接变异体 KLF6-SV1 的小干扰 RNA 作为胃癌的基因治疗。
Gastric Cancer. 2011 Oct;14(4):339-52. doi: 10.1007/s10120-011-0049-x. Epub 2011 May 3.
6
The role of KLF6 and its splice variants in cancer therapy.KLF6及其剪接变体在癌症治疗中的作用。
Drug Resist Updat. 2009 Feb-Apr;12(1-2):1-7. doi: 10.1016/j.drup.2008.11.001. Epub 2008 Dec 18.
7
The KLF6 splice variant KLF6-SV1 promotes proliferation and invasion of non-small cell lung cancer by up-regultating PI3K-AKT signaling pathway.KLF6剪接变体KLF6-SV1通过上调PI3K-AKT信号通路促进非小细胞肺癌的增殖和侵袭。
J Cancer. 2019 Aug 29;10(22):5324-5331. doi: 10.7150/jca.34212. eCollection 2019.
8
Identification of miRNAs that specifically target tumor suppressive KLF6-FL rather than oncogenic KLF6-SV1 isoform.鉴定特异性靶向肿瘤抑制因子KLF6-FL而非致癌性KLF6-SV1亚型的微小RNA。
RNA Biol. 2014;11(7):845-54. doi: 10.4161/rna.29356. Epub 2014 Jun 12.
9
In vivo regulation of p21 by the Kruppel-like factor 6 tumor-suppressor gene in mouse liver and human hepatocellular carcinoma.小鼠肝脏和人肝细胞癌中Kruppel样因子6肿瘤抑制基因对p21的体内调控
Oncogene. 2007 Jun 28;26(30):4428-34. doi: 10.1038/sj.onc.1210223. Epub 2007 Feb 5.
10
Lnc-PKD2-2-3/miR-328/GPAM ceRNA Network Induces Cholangiocarcinoma Proliferation, Invasion and 5-FU Chemoresistance.长链非编码RNA-PKD2-2-3/miR-328/GPAM竞争性内源RNA网络诱导胆管癌增殖、侵袭及5-氟尿嘧啶化疗耐药
Front Oncol. 2022 Jul 29;12:871281. doi: 10.3389/fonc.2022.871281. eCollection 2022.

引用本文的文献

1
Upregulation of long non-coding RNA SNHG11 promotes apoptosis and its molecular mechanisms in human osteosarcoma U2OS cells.长链非编码RNA SNHG11上调促进人骨肉瘤U2OS细胞凋亡及其分子机制
Sci Rep. 2025 Jul 15;15(1):25472. doi: 10.1038/s41598-025-10470-8.
2
The splicing factor proline and glutamine rich promotes the growth of osteosarcoma via the c-Myc signaling pathway.富含脯氨酸和谷氨酰胺的剪接因子通过c-Myc信号通路促进骨肉瘤生长。
Am J Cancer Res. 2023 Jun 15;13(6):2488-2503. eCollection 2023.
3
The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer.

本文引用的文献

1
AKIP1 promotes glioblastoma viability, mobility and chemoradiation resistance via regulating CXCL1 and CXCL8 mediated NF-κB and AKT pathways.AKIP1通过调节CXCL1和CXCL8介导的NF-κB和AKT信号通路，促进胶质母细胞瘤的生存能力、迁移能力和放化疗抗性。
Am J Cancer Res. 2021 Apr 15;11(4):1185-1205. eCollection 2021.
2
Osteosarcoma, personalized medicine, and tissue engineering; an overview of overlapping fields of research.骨肉瘤、个性化医疗和组织工程；研究重叠领域概述。
Cancer Treat Res Commun. 2021;27:100324. doi: 10.1016/j.ctarc.2021.100324. Epub 2021 Jan 27.
3
Surgical Advances in Osteosarcoma.
非编码 RNA 与可变剪接的相互作用：从调控机制到癌症的治疗意义。
Theranostics. 2023 Apr 23;13(8):2616-2631. doi: 10.7150/thno.83920. eCollection 2023.
骨肉瘤的外科进展
Cancers (Basel). 2021 Jan 21;13(3):388. doi: 10.3390/cancers13030388.
4
Osteosarcoma Pathogenesis Leads the Way to New Target Treatments.成骨肉瘤发病机制为新靶点治疗开辟道路。
Int J Mol Sci. 2021 Jan 15;22(2):813. doi: 10.3390/ijms22020813.
5
Osteosarcoma: A comprehensive review of management and treatment strategies.骨肉瘤：管理和治疗策略的全面综述。
Ann Diagn Pathol. 2020 Dec;49:151654. doi: 10.1016/j.anndiagpath.2020.151654. Epub 2020 Oct 25.
6
Two Sides of the Same Coin: The Roles of KLF6 in Physiology and Pathophysiology.两面一体：KLF6 在生理学和病理生理学中的作用。
Biomolecules. 2020 Sep 28;10(10):1378. doi: 10.3390/biom10101378.
7
Long Non-Coding RNA-Ribonucleoprotein Networks in the Post-Transcriptional Control of Gene Expression.基因表达转录后调控中的长链非编码RNA-核糖核蛋白网络
Noncoding RNA. 2020 Sep 17;6(3):40. doi: 10.3390/ncrna6030040.
8
A Review of T-Cell Related Therapy for Osteosarcoma.T 细胞相关疗法治疗骨肉瘤的研究进展。
Int J Mol Sci. 2020 Jul 10;21(14):4877. doi: 10.3390/ijms21144877.
9
Adjuvant and Neoadjuvant Chemotherapy for Osteosarcoma: A Historical Perspective.骨肉瘤的辅助和新辅助化疗：历史观点。
Adv Exp Med Biol. 2020;1257:1-10. doi: 10.1007/978-3-030-43032-0_1.
10
Epidemiology and Risk Factors of Osteosarcoma.骨肉瘤的流行病学和危险因素。
Cancer Invest. 2020 May;38(5):259-269. doi: 10.1080/07357907.2020.1768401. Epub 2020 Jun 1.