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长链非编码RNA SCIRT通过上调基质金属蛋白酶-2/-9促进宫颈癌细胞的增殖、迁移和侵袭能力。

The IncRNA SCIRT Promotes the Proliferative, Migratory, and Invasive Properties of Cervical Cancer Cells by Upregulating MMP-2/-9.

作者信息

Guan Chunfeng, Wang Beibei, Dong Qixiu

机构信息

Prenatal Diagnosis in Obstetrics and Gynecology, The Second Hospital of Anhui Medical University, Hefei, Anhui, China.

Department of Obstetrics and Gynecology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu, China.

出版信息

J Oncol. 2022 Aug 8;2022:3448224. doi: 10.1155/2022/3448224. eCollection 2022.

Abstract

OBJECTIVE

The morbidity and mortality of cervical cancer (CC) rank the fourth-most common among cancers in females, seriously threatening women's health and affecting their quality of life. However, the molecular mechanism of CC development remains poorly understood. This study investigates the role of lncRNA SCIRT in the development of CC.

METHODS

The expression profile of long noncoding RNA stem cell inhibitory RNA transcript (lncRNA SCIRT) in CC ( = 34), tumor-adjacent tissue, and CC cell culture was determined through fluorescence quantitative PCR. The knockdown /overexpressed lncRNA SCIRT vectors were constructed and transfected into cells, and the effects of knockdown or overexpression of lncRNA SCIRT on the proliferative, invasive, and migratory properties of CC cells were determined through Cell Counting Kit-8 (CCK-8), colony forming, and Transwell experiments. Western blot was employed to determine the knockdown/overexpression efficiency of SCIRT and its role on the expression of proteins (e-cadherin, n-cadherin, vimentin, matrix metalloproteinase (MMP)-9 and MMP-2) in CC cells. Finally, SCIRT knockdown on the proliferative ability for CC cells was determined through tumorigenic experiment in nude mice.

RESULTS

LncRNA SCIRT was highly expressed in CC tissues and cells, and significantly linked with clinical/pathology-based characteristics of patients, including Federation Internationale of Gynecologie and Obstetrigue (FIGO) stage, tumor dimensions, and lymph-node metastasis. SCIRT knockdown markedly reduced CC proliferative, colony forming, and invasive properties, while overexpressing SCIRT promoted the proliferative and invasive properties of CC. Western blotting analysis demonstrated that SCIRT knockdown upregulated e-cadherin and downregulated n-cadherin, vimentin, MMP-9, and MMP-2. Meanwhile, overexpressing SCIRT of lncRNA SCIRT had the opposite effect. Tumorigenic experiment showed that SCIRT knockdown could markedly reduce CC proliferative property the nude mouse.

CONCLUSION

LncRNA SCIRT was highly expressed in CC clinical cases. Knockdown/overexpressing SCIRT affected CC proliferative/invasive properties. Hence, lncRNA SCIRT is a promising drug-target and a new biological diagnostic molecule for CC patients.

摘要

目的

宫颈癌(CC)的发病率和死亡率在女性癌症中位列第四,严重威胁女性健康并影响其生活质量。然而,CC发生发展的分子机制仍知之甚少。本研究探讨长链非编码RNA(lncRNA)干细胞抑制性RNA转录本(SCIRT)在CC发生发展中的作用。

方法

通过荧光定量PCR检测长链非编码RNA干细胞抑制性RNA转录本(lncRNA SCIRT)在CC组织(n = 34)、癌旁组织及CC细胞培养物中的表达谱。构建lncRNA SCIRT的敲低/过表达载体并转染至细胞中,通过细胞计数试剂盒-8(CCK-8)、集落形成及Transwell实验检测lncRNA SCIRT敲低或过表达对CC细胞增殖、侵袭和迁移能力的影响。采用蛋白质印迹法检测SCIRT的敲低/过表达效率及其对CC细胞中蛋白质(E-钙黏蛋白、N-钙黏蛋白、波形蛋白、基质金属蛋白酶(MMP)-9和MMP-2)表达的作用。最后,通过裸鼠成瘤实验检测SCIRT敲低对CC细胞增殖能力的影响。

结果

lncRNA SCIRT在CC组织和细胞中高表达,且与患者的临床/病理特征显著相关,包括国际妇产科联盟(FIGO)分期、肿瘤大小和淋巴结转移。SCIRT敲低显著降低了CC的增殖、集落形成和侵袭能力,而过表达SCIRT则促进了CC的增殖和侵袭能力。蛋白质印迹分析表明,SCIRT敲低下调了N-钙黏蛋白、波形蛋白、MMP-9和MMP-2,同时上调了E-钙黏蛋白。此外,lncRNA SCIRT过表达则产生相反的效果。成瘤实验表明,SCIRT敲低可显著降低裸鼠体内CC的增殖能力。

结论

lncRNA SCIRT在CC临床病例中高表达。敲低/过表达SCIRT会影响CC的增殖/侵袭能力。因此,lncRNA SCIRT是一种有前景的药物靶点和CC患者的新型生物诊断分子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5861/9377974/e63cb228bb4d/JO2022-3448224.001.jpg

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