Table 3.
microRNA can regulate cell death pathways in oral cancer.
| miRNAs | Expression | Cancer cell | Target of miRNA | Inhibition/Induction of Cell Death | Sample type | Note | Ref |
|---|---|---|---|---|---|---|---|
| miR-486-3p | Down | Oral squamous cell carcinoma (OSCC) | DDR1 | Induction of apoptosis | Human (OSCC tissue, n= 40), In vitro (OEC-M1 and TW2.6 cells) | Overexpression of miR-486-3p can induces apoptosis by regulating DDR1 expression. | (1) |
| miR-4282 | Down | OSCC | LIN28B | Induction of apoptosis | Human (OSCC tissue, n=72), In vivo (mice), In vitro (SCC15 and TSCCA cells) | miR‐4282 induces the apoptosis of OSCC cells through a decreased expression level of ZBTB2 via targeting LIN28B. | (2) |
| miR-17 | – | Human tongue squamous cell carcinoma (TSCC) | – | Inhibition of apoptosis |
In vitro (CAL-27 cells), In vivo (Xenograft tumor model (BALB/c nude mice)) |
MiR-17 suppresses the induction of cisplatin-induced apoptosis. Suppression of miR-17 causes induction apoptosis and autophagy by STAT3 signaling. |
(3) |
| miR-17-5p | – | OSCC | – | – | In vitro (OC3 cells) | miR-17-5p increases (TRAIL R1, HIF-1α and cIAP-1) or decreases (p53, p21, FADD and TNF RI) apoptosis-related proteins in irradiated OC3 cell. | (4) |
| miR-27a | Up | TSCC | – | Inhibition of apoptosis | In vitro (Cal-27 cells and Clinical TSCC sample) | Decrease expression level of miR-27a lead to promote cell apoptosis in Cal-27 cells. | (5) |
| miR-145-5p | Down | TSCC and Oral cancer | – | Induction of apoptosis | Human (TSCC tissues), In vitro (SCC9 and Cal27 cell) |
Upregulation of miR-145-5p levels cause promote cell apoptosis. | (6, 7) |
| miR-183 | Up | TSCC | – | Inhibition of apoptosis | In vitro (SCC25 cell) | Downregulation of miR-183 levels lead to induction of apoptosis through decrease and increase expression level of casase-3 and BCL-xL, respectively. | (8) |
| miR-146a-5p | Up | OSCC | – | Inhibition of apoptosis | In vitro (SCC-9 cell) | The downregulation of miR-146a-5p levels leads to induces apoptosis in OSCC cells. | (9) |
| miR-149 | Down | OSCC | – | Induction of apoptosis | In vitro (PECAPJ41 and HSC-4 cells) | Inhibition of miR-149 significantly suppresses apoptosis and autophagy. | (10) |
| miR-155 | Up | Oral cancer cells | FoxO3a | Inhibition of apoptosis | In vitro (KB and KB/DDP cell line) | Inhibition of miR-155 significantly promotes apoptosis | (11) |
| miR-155 | Up | OSCC | p27Kip1 | Inhibition of apoptosis | Human (OSCC tissues, n=46), In vitro (Tca8113 cells) | Inhibition of miR-155 significantly promotes apoptosis od OSCC cells. | (12) |
| miR-378-3p/5p | Down | OSCC | KLK4 | Induction of apoptosis | Human (OSCC tissues, n=30), In vitro (KB and Tca8113 cells) | miR-378-3p/5p promotes apoptosis of OSCC through targeting KLK4 | (13) |
| miR-101-3p, miR-199b-5p |
Down | Oral cancer | BICC1 | Induction of apoptosis | Human (oral cancer tissues, n=62), In vitro (Tca8113, CAL-27, TSCCA, SCC-9) and In vivo (mice) | Overexpression of miR-199b-5p and miR-101-3p levels induces apoptosis by targeting BICC1 expression. | (14) |
| miR-214 | Up | Oral cancer | MAPK/ERK signaling pathway | Inhibition of apoptosis | In vitro (HB cell lines) | miR-214 suppresses apoptosis by MAPK/ERK signaling pathway. | (15) |
| miR-214 | Up | Oral cancer | RASSF5 | Inhibition of apoptosis | In vitro (KB cell) | Downregulation of miR-214 expression lead to inhibition of apoptosis by targeting RASSF5. | (16) |
| miR-139 | Down | Oral cancer | Akt signaling pathway | Induction of apoptosis | In vitro (Tca8113 cell) | Overexpression of miR-139 levels cause promote apoptosis through Akt signaling pathway. | (17) |
| miR-21−5p | Up | TSCC | PDCD4 | Inhibition of apoptosis | Human (TSCC, n= 40), In vitro (Cal 27 and SCC9 cells) | miR-21-5p inhibits apoptosis by targeting PDCD4 and regulating the PI3K/AKT/FOXO1 signaling pathway. | (18) |
| miR-21 | – | OSCC | – | Inhibition of apoptosis | In vitro (SCC15 and SCC25 cell) | miR-21 can inhibit apoptosis by up-regulating PTEN expression | (19) |
| miR-9 | Down | OSCC | – | Induction of apoptosis | Human (OSCC, n= 21), In vitro (Tca8113 cells) | Overexpression of miR-9 levels cause induction of apoptosis | (20) |
| miR-203 | Down | Oral cancer | Bmi-1 | Induction of apoptosis | In vitro (YD-38 cells) | Upregulation of miR-203 levels cause induction of apoptosis by targeting Bmi-1. | (21) |
| miR-203 | Down | Oral cancer | SEMA6A | Induction of apoptosis | In vitro (YD-38 cells) | miR-203 promotes apoptosis by targeting SEMA6A. | (22) |
| miR-4513 | Up | OSCC | CXCL17 | Inhibition of apoptosis | In vitro (Tca8113 and CAL-27) | Downregulation of miR-4513 levels promotes apoptosis. | (23) |
| miR-376c-3p | Down | OSCC | HOXB7 | Induction of apoptosis | Human (OSCC, n= 49), In vitro (SCC-25 cells) | Overexpression of miR-376c-3p induces the apoptosis of SCC-25 cells by targeting HOXB7. | (24) |
| miR-375 | Down | OSCC | IGF-1R | Induction of apoptosis | Human (OSCC, n= 44), In vitro (SCC-4) | miRNA-375 enhances apoptosis by targeting IGF-1R. | (25) |
| miR-124 | – | OSCC | – | Induction of apoptosis | In vitro (KB and SCC9 cell) | Icaritin promotes mitochondrial apoptosis via increasing expression level of miR-124. | (26) |
| miR-26a | – | Oral cancer cells | Mcl-1 | Induction of apoptosis | In vitro (KB cell) | Metformin promotes apoptosis through decreasing Mcl-1 expression by miR-26a. | (27) |
| miR−221/222 | Up | OSCC | PTEN | Inhibition of apoptosis | In vitro (CAL27 and HSC6 cell) | miR−221/222 inhibits apoptosis by targeting PTEN. | (25) |
| miR-448 | Up | OSCC | MPPED2 | Inhibition of apoptosis | Human (OSCC, n= 15), In vitro (Cal−27 and Scc−9) | miR−448 inhibits apoptosis by targeting MPPED2. | (28) |
| miR-29a | Down | OSCC | MMP-2 | Induction of apoptosis | Human (OSCC, n= 15), In vitro (SCC-4) | miR−29a induces apoptosis by targeting MMP-2. | (29) |
| miR-29b | Down | TSCC | Sp1 | Induction of apoptosis | Human (OSCC, n= 40), In vitro (CAL27 cells) | Upregulation of miR-29b level cause promotes apoptosis in TSCC cells by regulating PTEN–AKT signaling pathway | (30) |
| miR-29a | Down | TSCC | Wnt/β-catenin pathway | Induction of apoptosis | Human (OSCC, n= 103), In vitro (HOK, SCC-25 cells) | Overexpression of miR−29a induces apoptosis by regulating Wnt/β-catenin pathway. | (31) |
| miR-9 | Down | OSCC | CXCR4 | Induction of apoptosis | In vitro (Tca8113 and SCC-9 cell) | Upregulation of miR-9 level cause promotes apoptosis in OSCC cells by targeting CXCR4 | (27) |
| miR-218 | – | OSCC | mTOR pathway | Induction of apoptosis | In vitro (OSCC cell line) | Overexpression of miR-218 reduces OSCC cell growth by caspase-mediated apoptosis. | (32) |
| miR-17-5p | Down | OSCC | p21 | Induction of apoptosis | In vitro (OC3 cells) | Overexpression of miR-17-5p mediated by radiation treatment leads to induction of apoptosis by downregulation of p21 levels. | (33) |
| miR-1179 | Up | Oral cancer cells | – | Inhibition of autophagy | In vitro (SCC-4, SCC-9, SCC-15 and SCC-25) | Inhibition of miR-1179 induces autophagy by regulation of MEK/ERK and PI3K/AKT signaling pathways. | (29) |
| miR-617 | Down | OSCC | SERPINE1 | Induction of apoptosis | In vitro (SCC-090 and PE/CA-PJ41) | Overexpression of miR-617 induces apoptosis of OSCC cells by negative regulation of SERPINE1. | (34) |
| miR-133a | Down | OSCC | CTBP2 | Induction of apoptosis | Human (OSCC, n= 40), In vitro (UT-SCC-15 and CAL-27) | Overexpression of miR-133a induces apoptosis of OSCC cells by the suppression of CTBP2. | (35) |
| miR-149-3p | Down | OSCC | AKT2 | Induction of apoptosis | In vitro (Cal27 and SCC-9) | miR-149-3p combined with Fluorouracil shows an additive effect on the OSCC cells apoptosis through targeting AKT2. | (36) |
| miR-198 | Down | OSCC | – | Induction of apoptosis | In vivo (mice), In vitro (Cal-27 and SCC-9 cells) | Overexpression of miR-198 induces the apoptosis of OSCC cells. | (37) |
| miR-487-3p | Down | OSCC | PPM1A | Induction of apoptosis | Human (OSCC, n= 20), In vitro (CAL-27 and TCA8113) | miR-487-3p induces apoptosis of OSCC cell by targeting PPM1A. | (38) |
| miR−196a | Up | OSCC | FOXO1 | Inhibition of apoptosis | In vitro (SCC9 cell) | Decrease the expression level of miR-196a induces apoptosis of SCC9 cell via regulating FOXO1 expression. | (39) |
| miR-103a-3p | Up | OSCC | RCAN1 | Inhibition of apoptosis | In vitro (TSCCA and TCA8113 cells) | Inhibition of miR-103a-3p induces the apoptosis of OSCC cells by targeting RCAN1. | (40) |
| miR-195 | Down | OSCC | – | Induction of apoptosis | In vitro (OSCC-15/DDP cells) | Overexpression of miR-195 induces apoptosis of OSC-15/DDP cells by regulating MEK1. | (18) |
| miR-92b | Up | OSCC | – | Inhibition of apoptosis | In vitro (CAL-27) | Inhibition of miR-92b induces the apoptosis of OSCC cells. | (41) |
| miR-101 | Down | OSCC | TGF-βR1 | Inhibition of apoptosis | In vitro (SCC-9 and Tca8113) | miR-101 induces apoptosis of OSCC cells through targeting TGF-βR1. | (42) |
| miR-22 | Down | OSCC | WNT1 | Induction of apoptosis | Human (OSCC, n=50) In vitro (Tca8113 and SAS) |
miR-22 promotes apoptosis of OSCC cells via targeting WNT1. | (43) |
| miR-18a-5p | Up | OSCC | TGF-β1/Smad2 pathway. | Inhibition of apoptosis | In vitro (SCC9 cell) | Downregulation of miR-18a-5p promotes apoptosis of SCC9 cell by regulation of TGF-β1/Smad2 pathway. | (44) |
| miR−543 | Up | OSCC | – | Inhibition of apoptosis | In vitro (SCC9, SCC25 and CAL27 cells) | miR−543 inhibits apoptosis of OSCC cell. | (45) |
| miR−199a−5p | Down | OSCC | IKKβ/NF−κB pathway | Induction of apoptosis | Human (OSCC, n= 60), In vitro (Tca8113 and SCC−4 cells) |
miR-199a-5p promoted apoptosis of OSCC cells through regulation of the NF−κB pathway via targeting IKKβ. | (46) |
| miR-16 | Down | OSCC | AKT3 and BCL2L2 | Induction of apoptosis | In vitro (SCC-25 and CAL-27 cells) | miR-16 can induce apoptosis of OSCC cells by decreasing AKT3 and BCL2L2 levels. | (47) |
| miR-186 | Down | OSCC | SHP2 | Induction of apoptosis | Human (OSCC tissue, n=14), In vitro (Tca8113 and SCC-25 cells) | Overexpression of miR-186 induces apoptosis of OSCC cells through ERK and AKT pathways by targeting SHP2. | (48) |
| miR-1-3p | Down | OSCC | DKK1 | Induction of apoptosis | In vitro (SCC-4 cells) | miR-1-3p promotes apoptosis of SCC-4 cells by regulating DKK1. | (49) |
| miR-626 | Up | OSCC | RASSF4 | Inhibition of apoptosis | Human (OSCC tissue, n=94), In vitro (f Ca9-22 and HSC2 cells) | miR-626 can inhibit apoptosis of OSCC cells by targeting RASSF4. | (50) |