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沉默 FTX 通过上调 miR-513b-5p 抑制胰腺癌细胞增殖和侵袭。

Silencing of FTX suppresses pancreatic cancer cell proliferation and invasion by upregulating miR-513b-5p.

机构信息

Department of Gastrointestinal Radiation Oncology, Cancer Hospital of Harbin Medical University, 150 Haping Road, Nangang District, Harbin City, Heilongjiang Province, 150081, P. R. China.

出版信息

BMC Cancer. 2021 Mar 18;21(1):290. doi: 10.1186/s12885-021-07975-6.

DOI:10.1186/s12885-021-07975-6
PMID:33736615
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7977589/
Abstract

BACKGROUND

Abnormal expression of long non-coding RNA (lncRNA) FTX (five prime to Xist), which is involved in X chromosome inactivation, has been reported in various tumors. However, the effect of FTX on the development of pancreatic cancer (PC) has not been elucidated. The purpose of this study was to explore the possible molecular mechanism of FTX in PC.

METHODS

Quantitative real-time PCR (qRT-PCR) was used to measure the expression levels of FTX and miR-513b-5p in PC cell lines. Proliferation and apoptosis of PC cells were determined by CCK-8, Edu assay, and flow cytometry. Invasion and migration ability of PC cells were detected by Transwell assay and scratch test. Bioinformatics analysis, luciferase reporter gene assay, and RNA immunoprecipitation (RIP) assay were used to verify the direct binding between FTX and miR-513b-5p. The xenotransplantation mouse model was established to explore the effect of FTX and miR-513b-5p on the PC tumor growth in vivo.

RESULTS

The expression levels of FTX were increased in PC cell lines, and silencing of FTX remarkably suppressed the invasion ability and cell viability. Besides, FTX could bind to miR-513b-5p as a competitive endogenous RNA, thus promoting the invasion and proliferation ability of PC cells. Moreover, knockdown of FTX inhibited the tumor growth and increased the expression levels of miR-513b-5p and apoptosis-related proteins in vivo.

CONCLUSIONS

FTX could directly combine with miR-513b-5p as a competitive endogenous RNA, thus promoting the occurrence and development of PC in vitro and in vivo.

摘要

背景

长链非编码 RNA(lncRNA)FTX(Xist 之前的五倍体)的异常表达与 X 染色体失活有关,已在各种肿瘤中报道。然而,FTX 对胰腺癌(PC)发展的影响尚未阐明。本研究旨在探讨 FTX 在 PC 中的可能分子机制。

方法

采用定量实时 PCR(qRT-PCR)检测 PC 细胞系中 FTX 和 miR-513b-5p 的表达水平。CCK-8、Edu 检测和流式细胞术测定 PC 细胞的增殖和凋亡。Transwell 检测和划痕试验检测 PC 细胞的侵袭和迁移能力。生物信息学分析、荧光素酶报告基因检测和 RNA 免疫沉淀(RIP)检测验证 FTX 与 miR-513b-5p 之间的直接结合。建立异种移植小鼠模型,探讨 FTX 和 miR-513b-5p 对体内 PC 肿瘤生长的影响。

结果

FTX 在 PC 细胞系中的表达水平升高,沉默 FTX 可显著抑制侵袭能力和细胞活力。此外,FTX 可以作为竞争性内源性 RNA 与 miR-513b-5p 结合,从而促进 PC 细胞的侵袭和增殖能力。此外,敲低 FTX 可抑制肿瘤生长并增加体内 miR-513b-5p 的表达水平和凋亡相关蛋白。

结论

FTX 可作为竞争性内源性 RNA 直接与 miR-513b-5p 结合,从而促进体外和体内 PC 的发生和发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/dd8b08b402e7/12885_2021_7975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/af27f67dd183/12885_2021_7975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/3e5ef64905c8/12885_2021_7975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/a35bfd5ea8c5/12885_2021_7975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/7853d5d953d6/12885_2021_7975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/fea17c7ba3f8/12885_2021_7975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/dd8b08b402e7/12885_2021_7975_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/af27f67dd183/12885_2021_7975_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/3e5ef64905c8/12885_2021_7975_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/a35bfd5ea8c5/12885_2021_7975_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/7853d5d953d6/12885_2021_7975_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/fea17c7ba3f8/12885_2021_7975_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/211c/7977589/dd8b08b402e7/12885_2021_7975_Fig6_HTML.jpg

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