The role of miRNAs in cancer was first reported by Calin et al. in chronic lymphocytic leukaemia [
17]. Subsequently, a plethora of studies strongly correlated the deregulated expression of miRNAs in the hallmarks of cancer [
18]. Diverse cellular mechanisms contribute to miRNA deregulation in cancer, and genetic changes [
19], aberrant DNA methylation [
20] and histone acetylation [
21] have been attributed to miRNA deregulation. Importantly, cancer-related transcription factors such as myc [
22] and p53 [
23] have been shown to influence miRNA expression. Additional mechanisms including alternative splicing, polyadenylation and mutations in miRNA processing machinery may also hamper miRNA maturation [
24]. Aberrant loss or gain of miRNAs contributes to initiation, progression, metastasis and drug resistance of a wide spectrum of cancers. Depending on the genes and/or pathways they affect, miRNAs can act as tumour suppressors or oncogenes in a tissue-specific manner. For example, let-7 family miRNAs are known to be tumour suppressors. Downregulation of let-7 expression has been reported in head, neck, lung, breast, ovarian and prostate cancers [
25]. Let-7 negatively regulates oncogenes such as KRAS, c-MYC, CDK6, HOXA9, TGFBR1, BCL-XL and MAP4K3, thereby promoting anti-oncogenic pathways [
26]. Similarly, miR-34 family [
27], miR-223 [
28], miR-143/145 cluster [
29,
30] and miR-204 [
31] are commonly downregulated in various cancers; interestingly, reconstitution of respective miRNAs in these studies significantly reduced tumour growth. Interestingly, miR-214 is oncogenic in osteosarcoma [
32] and nasopharyngeal cancer [
33], whereas it appears to be a tumour suppressor in glioma [
34] and colorectal cancer [
35]. Similarly, miR-125b displays an oncogenic phenotype in colon and haematopoietic cancers, whereas it acts as a tumour suppressor in breast cancer and hepatocellular carcinoma [
36]. Additional miRNAs, namely miR-17/92 cluster, miR-21, miR-155, miR-221, miR-222 and miR-9 are upregulated in various cancers [
37]. Elevated miR-17/92 levels caused oncogenic activation of PI3K and NF-kB signalling in lymphomas [
38]. MiR-21 overexpression has a causal role in tumourigenesis of pre-B cell lymphomas [
39]. MiR-155 inhibition restored expression of tumour suppressor TP53INP1 and inhibited tumour development in breast cancer [
40]. The intimate role of miRNAs in tumour metastasis, drug resistance and cancer stemness has been discussed elsewhere [
41]. A more recent update on the role of miRNAs in various cancers has been tabulated (Table
1). Taken together, dysregulated miRNA expression appears to influence various hallmarks of cancer. A comprehensive understanding of miRNA biology in carcinogenesis can possibly pave novel routes for anti-cancer therapy.
Table 1
A list of miRNAs involved in various cancer types. Corresponding functional role (phenotype) and validated targets (targets) are shown in separate columns
Lung cancer | miR-132/212 | TS | CyclinD1 | |
(NSCLC) | miR-124 | TS | SOX8 | |
miR-126 | TS | VEGF-PI3K-Akt-MRP1 | |
miR-181 | TS | Bcl2 | |
miR-34a | TS | TGFβR2 | |
miR-145 | TS | Oct-4 | |
miR-21 | OG | PDCD4 | |
miR-137 | PM | SLC22A18 | |
Gastro-intestinal cancers |
Gastric cancer | miR-335 | TS | RASA1 | |
miR-374b-5p | OG | RECK | |
miR-490-3p | OG | SMARCD1 | |
miR-199a-3p | OG | ZHX1 | |
Colorectal cancer | miR-185 | TS-PM | STIM1 | |
miR-92a | OG-PM | PTEN | |
miR-7 | TS-PM | EGFR | |
Hepatocellular carcinoma | miR-9 | PM | | |
miR-150-5p | TS | MMP14 | |
miR-21 | OG-PM | AP1 | |
miR-122 | TS | Hnf4α-GALNT10-EGFR | |
miR-486-5p | TS | PIK3R1 | |
Esophageal cancer | miR-101, miR-127 | TS | MALAT1 | |
miR-126 | TS | DNMT1/ADAM9-EGFR | |
miR-27a | TS | K-Ras | |
Haematological cancers | | | | |
Lymphoma | miR-155-3p, | TS | LT-β | |
| miR-224 | TS-PM | CD59 | |
miR-17-92 | OG | Sin3b, Hbp1, Suv420h1, Btg1, Bim | |
Leukaemia | miR-486-5p | OG | AKT-FOXO1 | |
| miR-22 | OG | PTEN | |
| miR-638 | TS | CDK2 | |
Reproductive cancers |
Cervical cancer | miR-126 | TS-PM | PTEN | |
miR-21, Let-7a | OG/TS | STAT3 | |
miR-375 | DR | E-cadherin | |
Prostate cancer | miR-3195, miR-374b | TS | HIF-1α, HIF-2α and VEGF | |
miR-218 | TS | TPD52 | |
miR-449b | PM | | |
Breast cancer | miR-873 | TS-DR | ERα–CDK3 | |
miR-18b, miR-103, miR-107 and miR-652 | PM | | |
miR-7 | TS-DR | EGFR, Src kinase | |
Glioblastoma | miR-125a-5p | TS | TAZ | |
miR-155 | OG-DR | MAPK13 and MAPK14 | |
miR-449a | TS | MAZ | |
miR-148a | TS | Oct4, Sox-2 | |