Clinical significance of microRNA-148a in patients with early relapse of stage II stage and III colorectal cancer after curative resection.
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.
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.
Hsiang-Lin
HL
Tsai
I-Ping
IP
Yang
Ching-Wen
CW
Huang
Cheng-Jen
CJ
Ma
Chao-Hung
CH
Kuo
Chien-Yu
CY
Lu
Suh-Hang
SH
Juo
Jaw-Yuan
JY
Wang
D000368:Aged; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood / Q000378:metabolism*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging
C550570:MIRN148 microRNA, human; D035683:MicroRNAs
CI; CRC; DFS; OR; OS; PCR; RT-qPCR; cDNA; colorectal cancer; complementary DNA; confidence interval; disease-free survival; miRNA; micro-RNA; odds ratio; overall survival; polymerase chain reaction; reverse transcription-quantitative polymerase chain reaction