Background

Metastasis and chemo-resistance are still important factors that limit the overall efficacy of colorectal cancer treatment. Understanding the detailed molecular mechanism and identifying potential biomarkers are of great value in prognosis prediction and risk stratification.

Objective

We investigated the role of miR-582-5p in colorectal cancer pathogenesis, progression and chemo-resistance. Furthermore, we explored the underlying molecular mechanism of miR-582-5p in modulation of malignant behaviors of colorectal cancer cells.

Methods

Clinical samples and colorectal cancer cell lines were applied to explore miR-582-5p expression level and its significance on tumor cell metastasis and chemo-resistance. Transwell study and cellular survivability study were performed to explore the influences of miR-582-5p expression modulation on tumor cell chemo-resistance and invasion/migration. Dual-luciferase reporter gene assay was conducted to explore the influences of miR-582-5p on its target gene TNKS2.

Results

Colorectal cancer patients with lymph node or distal organ metastatic diseases exhibited significantly lower level of miR-582-5p. In vitro studies have indicated that miR-582-5p inhibition significantly increased migration and chemo-resistant capabilities of tumor cells. And dual-luciferase reporter gene assay demonstrated that miR-582-5p exhibited its influences on the biological behavior of tumor cells by targeting TNKS2.

Conclusions

Our study demonstrated for the first time that miR-582-5p played an important role for colorectal tumor cell metastasis and chemo-resistance. Our research also indicated that miR-582-5p and its target gene TNKS2 could be novel biomarkers for metastatic disease prediction, overall prognosis evaluation, as well as potential therapeutic target for colorectal cancer patients.

中文翻译：

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miR-582-5p 通过靶向 TNKS2 抑制结直肠癌细胞的迁移和耐药能力

背景

转移和化疗耐药仍然是限制结直肠癌治疗总体疗效的重要因素。了解详细的分子机制并识别潜在的生物标志物对于预后预测和风险分层具有重要价值。

客观的

我们研究了 miR-582-5p 在结直肠癌发病机制、进展和化疗耐药中的作用。此外，我们探讨了 miR-582-5p 在调节结直肠癌细胞恶性行为中的潜在分子机制。

方法

应用临床样本和结直肠癌细胞系探讨miR-582-5p表达水平及其对肿瘤细胞转移和化疗耐药的意义。进行了Transwell研究和细胞存活性研究，以探讨miR-582-5p表达调节对肿瘤细胞化学抗性和侵袭/迁移的影响。进行双荧光素酶报告基因检测，探讨miR-582-5p对其靶基因TNKS2的影响。

结果

患有淋巴结或远端器官转移性疾病的结直肠癌患者的 miR-582-5p 水平显着降低。体外研究表明，抑制 miR-582-5p 显着增加了肿瘤细胞的迁移和化学抗性能力。双荧光素酶报告基因检测表明，miR-582-5p通过靶向TNKS2对肿瘤细胞的生物学行为产生影响。

结论

我们的研究首次证明 miR-582-5p 在结直肠肿瘤细胞转移和化疗耐药中起重要作用。我们的研究还表明，miR-582-5p 及其靶基因 TNKS2 可能是转移性疾病预测、总体预后评估的新型生物标志物，以及结直肠癌患者的潜在治疗靶点。