MicroRNAs as diagnostic and prognostic biomarkers in colorectal cancer

Table 1 Overview of functions of microRNAs in colorectal cancer

MiRNA	Disease progression	Biomarker	Treatment
MiR-21	Increased miR-21 correlated with CRC cell proliferation, invasion, lymph node metastases and advanced clinical stage[11,23,24] MiR-21 keeps increasing during the process from precancerous polyps to early cancer[20] High expression of miR-21 associated with poor progress in the stage II/III Japanese[11,21] and stage II German cohorts[21], Hong Kong[25], Czech[26] and Danish[27,28] cohorts of CRC patients	Increased miR-21 as an indicator for poor OS and DFS in patients of Duke stage[29] Elevated miR-21 as a marker for lymph metastasis in patients of TNM stage[30] MiR-21 in serum[33] as a noninvasive marker to detect early stage of CRC	Decreased miR-21 sensitizes CRC cells to 5-FU-treatment[21]
MiR-29	Elevated miR-29a is significantly correlated with metastasis, especially liver metastasis[38,39,42] Upregulation of miR-29a associated with a better outcome at 12 mo[43,44] High miR-29b expression associated with higher 5-yr DFS and OS[48]	MiR-29a as a biomarker for early detection of CRC and prediction of survival[38,43,44] MiR-29b as a biomarker for 5-yr DFS and OS (stage III CRC)[48]
MiR-34a	Downregulation of miR-34a associated with CRC development[57] MiR-34a predicates recurrence of CRC patients[59] Increased miR-34b/c observed in more advanced tumors and associated with poor prognosis[60]	MiR-34a as a biomarker to predict recurrence of stage II and stage III CRC patients[59]	Increased miR-34a sensitizes CRC cells to 5-FU-treatment[58]
MiR-124a	High frequency of methylation of miR-124a in chronic inflammation and CRC[65,66] Methylation of miR-124a is emerging during oncogenesis in UC patients and could be used to estimate individual risk for cancer[71]	The methylation level of miR-124a as a factor for evaluating the risk of carcinogenesis in UC patients[71]
MiR-130b	High level of miR-130b in advanced tumor stages (III-IV), miR-130b-PPARγ axis plays a novel role in progressing towards more invasive CRC[77] MiR-130b inhibits CRC cells migration[75]	Increased miR-130b in advanced tumor stages[77]
MiR-139-3p	Decreased miR-139-3p in CRC tissues[82,83] Downregulation of miR-139-3p associated with poor survival, especially in patients with TNM stages I and II[82]	MiR-139-3p as a marker for poor survival[82] MiR-139-3p in plasma used for predicting occurrence of CRC[84]
MiR-155	High expression correlated with an advanced TNM stage and metastasis[85] Increased expression of postoperative miR-155 correlated with recurrence and metastasis of CRC[87]	MiR-155 as a prognostic maker for OS and DFS of CRC patients[11,86]
MiR-224	Increased expression of miR-224 associate with tumor growth[89] and metastasis of CRC[90] MiR-224 inhibits CRC cells migration[95]	MiR-224 as a predictor for the short-time relapse and shorter metastasis-free survival[90-93]	Suppression of miR-224 sensitizes CRC to chemoradiotherapy[94]
MiR-378	MiR-378 is up-regulated in CRC samples[96,97] and promotes cell survival, invasion, and angiogenesis[98,99] Expression of miR-378 is increased in plasma of CRC patient, and rapidly goes down within 4-6 mo after surgery[103] Decreased miR-378 in CRC tissues and cell lines is associated with increased the size of tumor, metastasis and short OS[104,105]	MiR-378 in plasma used to predict the occurrence of CRC[103] Reduction of miR-378 in CRC tissues as a predictor for short OS[104]

UC: Ulcerative colitis; CRC: Colorectal cancer; OS: Overall survival; DFS: Disease-free survival.