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评估 miR-1908-3p 作为一种新型乳腺癌血清生物标志物及其致癌功能和靶基因。

Evaluation of MiR-1908-3p as a novel serum biomarker for breast cancer and analysis its oncogenic function and target genes.

机构信息

Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou, China.

出版信息

BMC Cancer. 2020 Jul 10;20(1):644. doi: 10.1186/s12885-020-07125-4.

Abstract

BACKGROUND

Breast cancer is one of the most common tumors for women globally. Various miRNAs have been reported to play a crucial role in breast cancer, however the clinical significance of miR-1908-3p in breast cancer remains unclear. The present study aimed to explore the role of miR-1908-3p in breast cancer.

METHODS

The expression of miR-1908-3p was detected in 50 pairs of breast cancer tissues and adjacent normal tissues, 60 breast cancer patient serum and 60 healthy volunteer serum. The functional roles of miR-1908-3p in breast cancer cells such as proliferation, migration and invasion were evaluated using CCK8, SRB, wound healing and transwell chambers. In addition, bioinformatics tools were used to identify potential targets of miR-1908-3p.

RESULTS

The results showed that the expression of miR-1908-3p were increased in breast cancer tissues and serum compared with normal breast tissues and serum of healthy volunteers respectively. Furthermore, the young breast cancer patients and HER2-positive patients had a higher level of tissues' miR-1908-3p than elder breast cancer patients and HER2-negative patients, respectively. The young breast cancer patients had a higher level of serum miR-1908-3p than elder breast cancer patients, ROC analysis suggested that miR-1908-3p had the potential as a promising serum diagnostic biomarker of breast cancer. Up-regulation of miR-1908-3p promoted the cells proliferation, migration and invasion while knockdown of miR-1908-3p inhibited these processes in breast cancer cell MCF-7 and MDA-MB-231. The potential target genes of miR-1908-3p in breast cancer included ID4, LTBP4, GPM6B, RGMA, EFCAB1, ALX4, OSR1 and PPARA. Higher expression of these eight genes correlated with a better prognosis for breast cancer patients.

CONCLUSIONS

These results suggest that miR-1908-3p may exert its oncogenic functions via suppression of these eight genes in breast cancer.

摘要

背景

乳腺癌是全球女性最常见的肿瘤之一。已有多种 miRNA 被报道在乳腺癌中发挥关键作用,但 miR-1908-3p 在乳腺癌中的临床意义尚不清楚。本研究旨在探讨 miR-1908-3p 在乳腺癌中的作用。

方法

检测 50 对乳腺癌组织及其相应癌旁正常组织、60 例乳腺癌患者血清和 60 例健康志愿者血清中 miR-1908-3p 的表达。采用 CCK8、SRB、划痕愈合和 Transwell 小室实验评估 miR-1908-3p 在乳腺癌细胞增殖、迁移和侵袭中的功能作用。此外,还利用生物信息学工具预测 miR-1908-3p 的潜在靶基因。

结果

结果显示,与正常乳腺组织及健康志愿者血清相比,miR-1908-3p 在乳腺癌组织和血清中的表达均升高。此外,年轻乳腺癌患者和 HER2 阳性患者的组织 miR-1908-3p 水平高于年长乳腺癌患者和 HER2 阴性患者,年轻乳腺癌患者的血清 miR-1908-3p 水平高于年长乳腺癌患者。ROC 分析表明,miR-1908-3p 具有作为乳腺癌有前途的血清诊断生物标志物的潜力。上调 miR-1908-3p 促进乳腺癌细胞 MCF-7 和 MDA-MB-231 的增殖、迁移和侵袭,而下调 miR-1908-3p 则抑制这些过程。miR-1908-3p 在乳腺癌中的潜在靶基因包括 ID4、LTBP4、GPM6B、RGMA、EFCAB1、ALX4、OSR1 和 PPARA。这 8 个基因的高表达与乳腺癌患者的预后较好相关。

结论

这些结果表明,miR-1908-3p 可能通过抑制这些基因在乳腺癌中发挥致癌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7130/7350204/291405f5c7b4/12885_2020_7125_Fig1_HTML.jpg

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