*MicroRNAs (miRNAs) in Colorectal Cancer DOI: http://dx.doi.org/10.5772/intechopen.80828*

*Oncogenes and Carcinogenesis*

**miRNAs Expression Target genes** miR-15a Upregulate *Bcl-2*

miR-17-3p Upregulate *E2F*, *CDKN1A* miR-18a Upregulate *SMAD4*, *KRAS*

miR-24 Downregulate *Topoisomerase-1* miR-29a Upregulate *DNMT3* miR-31 Downregulate *WNT*, *β-catenin*

miR-20a Upregulate *BECN1*, *ATG16L1*, *SQSTM1* miR-21 Upregulate *PDCD4*, *PTEN*, *SPRY2*, *TPMI*

miR-34a Downregulate *SMAD4*, *FRAT1*, *Bcl-2*, *c-Met*

Let-7g Upregulate *KRAS*, *Cdk6*, *Cdc25*, *HMGA2*

miR-92a Upregulate *PHLPP2*, *VHL*, *Bim*

miR-106b Upregulate *P21*, *E2F1* miR-133a Downregulate *MCL1*, *BCL2L2* miR-143 Downregulate *Erk5*, *DNMT3*, *KRAS* miR-145 Downregulate *EGFR*, *IRS-1* miR-181b Downregulate *ATM* miR-203 Downregulate *ABL1*, *TP63* miR-223 Upregulate *STMN1* miR-302 Upregulate *GAB2*, *AKT2* miR-320a Downregulate *VDAC*, *STAT3*, *SOX4*

miR-335 Upregulate *RASA-1*

miR-422a Downregulate *TGF-β*, *CD73* miR-423-5p Downregulate *RFVT3* miR-601 Downregulate *PTP4A1* miR-760 Downregulate *PHLPP2*

miR-375 Downregulate *SLC7A11*, *IGFR1*, *SEC23A*

miR-19a/miR-19b Upregulate *PTEN*

**36**

*tyrosine phosphatase 4a1.*

**Table 1.**

hence, expression levels of miR-125p are associated with poor survival among CRC patients [69]. However, miR34 expression is a good prognostic marker. miR-34 is one of the targets of p53 protein and it increases miRNA expression. miR-34 then suppresses the expression of WNT pathway and epithelial mesenchymal transition (EMT)-related genes. Increase of miR-34b and miR-34c levels in stromal tissue is

*Simplified list of diagnostic miRNA markers for colorectal cancer (modified from Refs. [58, 59]).*

*Abbreviations: Bcl-2, B cell lymphoma-2; E2F, E2F transcription factor 1; CDKN1A, cyclin-dependent kinase inhibitor 1A; KRAS, Kirsten rat sarcoma viral oncogene homolog; PTEN, phosphotensin homolog; BECN1, Beclin 1; ATG16L1, autophagy-related 16 like 1; SQSTM1, sequestosome 1; PDCD4, programmed cell death 4; SPRY2, sprouty RTK signaling antagonist 2; DNMT3, DNA methyl transferase 3; FRAT1, WNT signaling pathway regulator; PHLPP2, PH domain leucine-rich repeat protein phosphatase 2; VHL, von Hippel-Lindau tumor suppressor; Cdk6, cyclin-dependent kinase 6; Cdc25, cell division cycle 25A; HMGA2, high-mobility group gene; P21, CDKN1A, cyclindependent kinase inhibitor 1A; E2F1, E2F transcription factor 1; MCL1, BCL2 family apoptosis regulator; BCL2L2, BCL2 like 2; EGFR, epidermal growth factor receptor; IRS-1, insulin receptor substrate 1; ATM, ataxia telangiectasia mutated; ABL1, v-abl Abelson murine leukemia viral oncogene homolog 1; TP63, tumor protein p63; STMN1, stathmin 1; GAB2, GRB2-associated binding protein 2; AKT2, v-akt murine thymoma viral oncogene homolog 2; VDAC, voltage-dependent anion channel; SOX4, SRY (sex-determining region Y)-box 4; SLC7A11, solute carrier family 7 member 11; IGFR1, insulin-like growth factor 1 receptor; TGF-β, transforming growth factor-beta; CD73, cluster of differentiation 73; RFVT3, known as SLC52A3 (solute carrier family 52 member 3); PTP4A1, protein*  leading to poor prognosis in colon cancer [70–72]. miR-122, miR-214, miR-372, miR-15b, let-7e, and miR-17 are other dysregulated miRNAs found in *TP53* mutated tumors [73]. miR-148-b and miR-221 are also important diagnostic markers associated with *p53* mutational status, and their overexpression is associated with worse prognosis [74, 75]. miR-143 and miR-145 are frequently downregulated in CRC and their one of the targets is KRAS mRNA; hence, they are important prognostic and predictive biomarkers in CRC [76, 77]. Let-7 role is one of the well-studied tumor suppressor miRNAs, which targets RAS. Let-7a expression is higher in *KRAS* mutated metastatic samples than normal mucosa or nonmetastatic disease [78]. Decrease Let-7b expression is worse prognostic marker, which is associated with recurrence and low overall survival of patients [79]. Furthermore, decrease in miR-487b levels is associated with liver metastasis in CRC patients [80]. Not only KRASassociated miRNAs act as tumor suppressor, some of them are acting oncogenic in prognosis. miR-200 and miR-221 are downstream miRNAs of RAS pathway, and high expression of these miRNAs is related with worse prognosis [81].

Furthermore, exosome-containing miRNAs (miR-17/92 cluster and miR-19a cluster) are evaluated as biomarkers for early diagnosis and high recurrence in patients with CRC [82]. miR-21-5p, miR-29-3p, and miR-148-3p levels were studied in CRC samples and show that dysregulation in these miRNAs is associated with high mortality risk [83].
