Table 1. Summary of the reported oncogenic or tumor suppressor functions of miR-9 and 9* in human cancer.
Tumor types and functions affected are listed in alphabetical order. It is indicated whether miR-9 levels are increased (↑) or decreased (↓) together with a list of direct targets when miR-9 or 9* is expressed or re-introduced in the given cell type. The information about the possible pathways involved has been added according to the literature based on the reported targets.
| Function | Apoptosis | Autophagy | Cell frequency | Chemo/drug resistance | Differentiation | Invasion | Metastasis | Migration | Proliferation | Self-renewal | Tumori-genicity | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tumor | Cell type | Feature | |||||||||||
| BC | ER+ | Direction | ↑ | ↓ | |||||||||
| Target | ESR1 | TUG1 | |||||||||||
| Pathway* | ER signaling ERK |
||||||||||||
| Metastatic | Direction | ↑ | ↑ | ↑ | |||||||||
| Target |
LIFR CDH1 |
LIFR CDH1 FOXO1 |
LIFR CDH1 FOXO1 |
||||||||||
| Pathway | Ras ERK E-cadherin |
Ras ERK E-cadherin PI3K/AKT |
Ras ERK E-cadherin PI3K/AKT |
||||||||||
| TNBC | Direction | ↓ | ↓ | ||||||||||
| Target |
MTHFD2 NOTCH1 |
MTHFD2 NOTCH1 |
|||||||||||
| Pathway | ERK NOTCH1 |
ERK NOTCH1 |
|||||||||||
| GBM | CD133+ | Direction | # | ↑↑ | |||||||||
| Target |
JAK1 JAK3 |
CAMTA1 CAMTA1 |
|||||||||||
| Pathway | ERK JAK/STAT EGFR PI3K/AKT |
||||||||||||
| Cell lines | Direction | ↑ | ↓ | ||||||||||
| Target | NF1 |
CREB STMN1 |
|||||||||||
| Pathway | EGFR ERK Ras |
NOTCH1 JAK/STAT EGFR ERK |
|||||||||||
| Chemo-resistant | Direction | ↑↓ | ↓ | ↓ | |||||||||
| Target |
PTCH1 SOX2 |
SOX2 | SOX2 | ||||||||||
| Pathway | ERK Wnt |
ERK Wnt |
ERK Wnt |
||||||||||
| ΔEGFR | Direction | ↓ | |||||||||||
| Target | FOXP1 | ||||||||||||
| Pathway | Wnt | ||||||||||||
| CC | CA | Direction | ↓ | ↓ | ↓ | ||||||||
| Target | IL6 | IL6 | IL6 | ||||||||||
| Pathway | JAK/STAT ERK |
JAK/STAT ERK |
JAK/STAT ERK |
||||||||||
| CSCC | Direction | ↓ | ↑ | ↑ | |||||||||
| Target |
ALCAM FSTL1 |
||||||||||||
| Pathway | CAM | ||||||||||||
| HM | ALL | Direction | ↓↓ | ||||||||||
| Target |
FGFR1 CDK6 |
||||||||||||
| Pathway | ERK Ras PI3K/AKT |
||||||||||||
| AML | Direction | ↓ | ↑↓ | ↑↓ | ↑ | ||||||||
| Target |
RYBH RHOH HES1 |
LIN28B/HMGA2 ERG |
UBASH3B LIN28B/HMGA2 RYBH RHOH HES1 |
RYBH RHOH |
|||||||||
| Pathway | ERK AKT NOTCH1 |
Wnt | ERK AKT NOTCH1 Wnt |
ERK | |||||||||
| HL | Direction | ↓ | |||||||||||
| Target | PRDM1 | ||||||||||||
| Pathway | TP53 NF-kappaB |
||||||||||||
| MM | Direction | ↓ | |||||||||||
| Target | IGF2BP3 | ||||||||||||
| Pathway | IGF2BP | ||||||||||||
| WM | Direction | ↑ | ↑ | ↓ | |||||||||
| Target |
HDAC4 HDAC5 |
HDAC4 HDAC5 |
HDAC4 HDAC5 |
||||||||||
| Pathway | JAK/STAT NOTCH1 HDAC |
JAK/STAT NOTCH1 HDAC |
JAK/STAT NOTCH1 HDAC |
||||||||||
| SCC | Oral | Direction | ↓ | ||||||||||
| Target | CCND1 | ||||||||||||
| Pathway | ERK JAK/STAT AKT Wnt |
||||||||||||
| Skin | Direction | ↑ | ↑ | ↑ | |||||||||
| Target | CTNNA1 | CTNNA1 | CTNNA1 | ||||||||||
| Pathway | Wnt ERK E-cadherin |
Wnt ERK E-cadherin |
Wnt ERK E-cadherin |
||||||||||
*: Possible affected target-related pathways according to www.genecards.org.
#: miR-9 has been reported to influence the direction of differentiation – it promotes oligoneural and suppresses more aggressive mesenchymal phenotype.
Functions attributed to miR-9* are marked in red.
Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; BC, breast cancer; CA, cervical adenocarcinoma; CC, cervical cancer; CSCC, cervical squamous cell carcinoma; ΔEGFR, mutant epidermal growth factor receptor; ER, estrogen receptor; GBM, glioblastoma multiforme; HL, Hodgkin lymphoma; HM, hematological malignancies; MM, multiple myeloma; SCC, squamous cell carcinoma; TNBC, triple-negative breast cancer; WM, Waldenström macroglobulinemia.