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LINC00346 通过竞争性结合 miRNA-101-5p/MMP9 加速结直肠癌的恶性进展。

LINC00346 accelerates the malignant progression of colorectal cancer via competitively binding to miRNA-101-5p/MMP9.

机构信息

Department of Gastrointestinal and Colorectal Surgery, The First Hospital of Jilin University, Changchun, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6639-6646. doi: 10.26355/eurrev_202006_21650.

DOI:10.26355/eurrev_202006_21650
PMID:32633353
Abstract

OBJECTIVE

To clarify the promotive effect of LINC00346 on the malignant progression of colorectal cancer (CRC) by mediating miRNA-101-5p/MMP9 axis.

PATIENTS AND METHODS

Expression pattern of LINC00346 in 46 paired CRC tissues and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between LINC00346 level and prognosis of CRC patients was analyzed, and the LINC00346 level in CRC cell lines was examined as well. Subsequently, potential influences of LINC00346 on cellular behaviors of CRC cells were evaluated through cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Finally, Dual-Luciferase reporter gene assay was conducted to verify the binding relationship between LINC00346 and miRNA-101-5p/MMP9.

RESULTS

LINC00346 was upregulated in CRC tissues and cell lines. Compared with CRC patients with low level of LINC00346, those with high level suffered a poorer prognosis, and higher metastatic rates (lymph node metastasis and distant metastasis). Transfection of sh-LINC00346 attenuated proliferative, migratory, and invasive abilities of CRC cells. In addition, LINC00346 was confirmed to bind to miRNA-101-5p, and the latter was binding to MMP9. Moreover, the overexpression of miRNA-101-5p decreased colony number, viability, and numbers of migratory and invasive cells.

CONCLUSIONS

LINC00346 is upregulated in CRC and correlated with metastasis and poor prognosis of CRC. LINC00346 accelerates the malignant progression of CRC via targeting miRNA-101-5p/MMP9.

摘要

目的

通过介导 miRNA-101-5p/MMP9 轴,阐明 LINC00346 对结直肠癌(CRC)恶性进展的促进作用。

患者和方法

通过实时定量聚合酶链反应(qRT-PCR)测定 46 对 CRC 组织和相邻正常组织中 LINC00346 的表达模式。分析 LINC00346 水平与 CRC 患者预后的相关性,并检测 CRC 细胞系中的 LINC00346 水平。随后,通过细胞计数试剂盒-8(CCK-8)、集落形成、Transwell 和划痕愈合实验评估 LINC00346 对 CRC 细胞细胞行为的潜在影响。最后,通过双荧光素酶报告基因实验验证 LINC00346 与 miRNA-101-5p/MMP9 之间的结合关系。

结果

LINC00346 在 CRC 组织和细胞系中上调。与 LINC00346 低水平的 CRC 患者相比,高水平的患者预后较差,转移率(淋巴结转移和远处转移)较高。sh-LINC00346 的转染减弱了 CRC 细胞的增殖、迁移和侵袭能力。此外,LINC00346 被证实与 miRNA-101-5p 结合,后者与 MMP9 结合。此外,miRNA-101-5p 的过表达降低了集落数、细胞活力以及迁移和侵袭细胞的数量。

结论

LINC00346 在 CRC 中上调,并与 CRC 的转移和不良预后相关。LINC00346 通过靶向 miRNA-101-5p/MMP9 加速 CRC 的恶性进展。

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