Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Division of General Surgery Medicine, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Program of Bachelor of Health Beauty, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan.
Transl Res. 2013 Oct;162(4):258-68. doi: 10.1016/j.trsl.2013.07.009. Epub 2013 Aug 7.
Development of robust prognostic/predictive biomarkers in patients with colorectal cancer (CRC) is imperative for advancing treatment strategies for this disease. We aimed to determine whether expression status of microRNAs might be a simple and reliable biomarker to detect postoperative early relapse in patients with CRC after radical resection. We used microRNA arrays and identified that microRNA-148a (miRNA-148a) had substantially different expression levels in early and nonearly relapsed stage II and III CRC tissues. The validation study, which included 55 early relapsed patients and 55 nonearly relapsed patients, further confirmed overexpression of miRNA-148a in nonearly relapsed samples. Subsequently, we explored whether the serum level of miRNA-148a can be used to predict early CRC recurrence. The in vitro and in vivo effects of miRNA-148a were examined by cell proliferation, migration, and invasion, as well as cell cycles, and xenograft in null mice. Last, miRNA-148a was investigated as a potential biomarker for identifying early relapse. Cellular studies demonstrated that the overexpression of miRNA-148a inhibited colon cancer cell proliferation and migration but not invasion. The cell cycle studies also revealed that miRNA-148a caused an accumulation of the G2 population. Moreover, lower levels of miRNA-148a expression were associated with significantly shorter disease-free survival rates and poorer overall survival rates. This study showed that miRNA-148a can inhibit tumorigenesis and reduce the early recurrence of CRC. These findings suggest that miRNA-148a may have potential clinical applications for predicting the early relapse of patients with CRC after radical resection.
开发稳健的结直肠癌（CRC）预后/预测生物标志物对于推进该疾病的治疗策略至关重要。我们旨在确定微 RNA 的表达状态是否可能是一种简单可靠的生物标志物，用于检测接受根治性切除术后 CRC 患者的术后早期复发。我们使用 microRNA 阵列发现，microRNA-148a（miRNA-148a）在 II 期和 III 期 CRC 组织的早期和非早期复发阶段具有明显不同的表达水平。包括 55 例早期复发患者和 55 例非早期复发患者的验证研究进一步证实了非早期复发样本中 miRNA-148a 的过表达。随后，我们探讨了血清 miRNA-148a 水平是否可用于预测 CRC 的早期复发。通过细胞增殖、迁移和侵袭以及细胞周期和裸鼠异种移植，研究了 miRNA-148a 的体外和体内作用。最后，研究了 miRNA-148a 是否可以作为识别早期复发的潜在生物标志物。细胞研究表明，miRNA-148a 的过表达抑制结肠癌细胞的增殖和迁移，但不抑制侵袭。细胞周期研究还揭示了 miRNA-148a 导致 G2 群体的积累。此外，miRNA-148a 表达水平较低与疾病无进展生存率和总生存率显著降低相关。这项研究表明，miRNA-148a 可抑制肿瘤发生并降低 CRC 的早期复发。这些发现表明，miRNA-148a 可能具有预测 CRC 患者根治性切除术后早期复发的潜在临床应用。
