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长链非编码RNA LINC00346的沉默通过靶向微小RNA-148b抑制结直肠癌的肿瘤发生。

Silencing of Long Noncoding RNA LINC00346 Inhibits the Tumorigenesis of Colorectal Cancer Through Targeting MicroRNA-148b.

作者信息

Li Tao, Wang Benjun, Zhang Lianxiang, Cui Meng, Sun Bing

机构信息

Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan City, Shandong Province, 250014, People's Republic of China.

Department of Anorectal, Shandong Provincial Hospital of Traditional Chinese Medicine, Jinan City, Shandong Province 250014, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Apr 17;13:3247-3257. doi: 10.2147/OTT.S242715. eCollection 2020.

Abstract

PURPOSE

This study was aimed to explore the regulatory effect of long noncoding RNA LINC00346 (LINC00346) on colorectal cancer (CRC) and the potential molecular mechanisms.

METHODS

The expression of LINC00346 and microRNA-148b (miR-148b) in CRC tissues and cells was detected by qRT-PCR. LINC00346 was overexpressed and silenced in HT29 and HCT116 cells by the transfection of pcDNA-LINC00346 and si-LINC00346, respectively. The cell proliferation, migration, invasion, and apoptosis were analyzed by cell counting kit-8 (CCK-8), wound-healing, transwell, and flow cytometry assay, respectively. The targeting relationship between LINC00346 and miR-148b was predicted by TargetScan and determined by dual-luciferase reporter assay. A tumor xenograft model was established in mice to evaluate the tumor growth in vivo.

RESULTS

The expression of LINC00346 was up-regulated in CRC tissues and cells. The expression of LINC00346 was positively associated with the TNM stage, lymphoma metastasis and histological grade. Overexpression of LINC00346 promoted the proliferation, migration and invasion and inhibited the apoptosis of HT29 and HCT116 cells. MiR-148b was a target of LINC00346. Silencing of miR-148b reversed the anti-tumor effect of si-LINC00346 on CRC cells. Furthermore, silencing of LINC00346 inhibited the tumor growth in mice through up-regulating miR-148b.

CONCLUSION

Silencing of LINC00346 inhibited the proliferation, migration and invasion, and promoted the apoptosis of CRC cells through targeting miR-148b.

摘要

目的

本研究旨在探讨长链非编码RNA LINC00346(LINC00346)对结直肠癌(CRC)的调控作用及潜在分子机制。

方法

采用qRT-PCR检测CRC组织和细胞中LINC00346和微小RNA-148b(miR-148b)的表达。分别通过转染pcDNA-LINC00346和si-LINC00346在HT29和HCT116细胞中过表达和沉默LINC00346。分别采用细胞计数试剂盒-8(CCK-8)、伤口愈合、Transwell和流式细胞术分析检测细胞增殖、迁移、侵袭和凋亡情况。通过TargetScan预测LINC00346与miR-148b的靶向关系,并通过双荧光素酶报告基因检测进行确定。在小鼠中建立肿瘤异种移植模型以评估体内肿瘤生长情况。

结果

LINC00346在CRC组织和细胞中表达上调。LINC00346的表达与TNM分期、淋巴结转移和组织学分级呈正相关。LINC00346的过表达促进了HT29和HCT116细胞的增殖、迁移和侵袭,并抑制了其凋亡。miR-148b是LINC00346的靶标。miR-148b的沉默逆转了si-LINC00346对CRC细胞的抗肿瘤作用。此外,LINC00346的沉默通过上调miR-148b抑制了小鼠体内肿瘤的生长。

结论

LINC00346的沉默通过靶向miR-148b抑制了CRC细胞的增殖、迁移和侵袭,并促进了其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0bc4/7173865/67a8f1e61351/OTT-13-3247-g0001.jpg

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