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microRNA在肿瘤细胞耐药中的作用

The role of microRNAs in tumor cells chemoresistance

microRNA	Target genes	Effect	Ref
miR-24	DHFR	The single base mutation 829C-T in DHFR 3’UTR, interferes the normal pairing between miR-24 and DHFR’mRNA, which make the expression of dihydrofolate reductase increased, and cause the methotrexate resistant phenotype.	[24]
miR-519c	BCRP ABCG2	The ABCG2 3’UTR of the S1MI80 cell contained a 1, 500 bp deletion, which includes the miR-519c reactive sites. This mutation make the expression of the drug efflux pump gene: ABCG2 cann’t reduced, and cause the multidrug resistance phenotype.	[25]
Abnormal expression
miR-15a/16	BCL2	The overexpression of miR-15a/16 can reduce the expression of the tamoxifen-induced BCL2, and enhance the resistance of breast cancer cells to tamoxifen.	[26]
miR-20	BNIP2	miR-20 can modify the sensitivity of colorectal cancer cell lines SW620, SW480 to 5-FU, oxaliplatin and teniposide, overexpression of miR-20 induced SW480 drug-resistance, downexpression of it can increase the drug-sensitivity of SW620.	[27]
miR-21	BCL2 MMR BCL2 PTEN PI3K/Akt	The overexpression of miR-21 could interfere the colorectal cancer cells G/M arrest and apoptosis induced by 5-FU, that drug-resistant appears by reducing the expression of mutated mismatch repair gene MMR. The overexpression of miR-21 mediates the BCL2/PTEN expression, which caused the DDP-resistance of NSCLC cell. The overexpression of miR-21 can reactivate the expression of tumor suppressor gene PTEN and reduces the activation of PI3K/AKT/mTOR pathway, then increase the sensitivity of pancreatic cancer cells to gemcitabine. Abnormal expression of miR-21 could lead the sensitive response of CML chronic myeloid leukemia cell line K562 to the DNR by changing PTEN expression directly by PI3K/AKT pathway.	[28-32]
miR-27a	HIPK2, MDR1, P-gp	The overexpression of miR-27a which by regulating the target gene of HIPK2, could regulate the expression of MDR1 and P-gp indirectly, which influence ovarian cancer resistant to paclitaxel.	[33]
miR-34	BCL2 CCND1 MAGE-A HuR SIRT1	miR-34 suppressed the expression of target genes: BCL2/CCND1, which is leading to the resistance of MCF-7 to docetaxel. The overexpression of miR-34 suppress the expression of MAGE-A, then increasing the expression of P53, and upregulate the expression of miR-34 by positive feedback regulation mechanism, which increases the sensitivity of tumor cells to mitomycin and cisplatin. The overexpression of miR-34 could downregulate the expression of SIRT1 and BCL2 directly or by suppressing the expression of HuR, and weaken the resistance hormone-independent prostate cancer PC3 cells to paclitaxel.	[34-36]
miR-34a	MYC Sirt1/E2F3	The low-expression of miR-34a can increase the expression of myc, and transform the sensitivity of P493-6 cells to brotezomib. Overexpression of miR-34a can antagonist the apoptosis induced by bortezomib. The overexpression of miR-34a can reverse the drug-resistance of DLD-1 cells by suppressing the expression of Sirt1/E2F3.	[37, 38]
miR-199a-3p	Target of rapamycin c-Met	miR-199a-3p can affect the sensitivity of hepatocellular carcinoma cells to doxorubicin by direct role in the target of rapamycin and c-Met, and maintain the low level expression of miR-199a-3p could improve the therapeutic effect of doxorubicin.	[39]
miR-125	Bak1	The high-level expression of miR-125 endue the tolerance of breast cancer cells to docetaxel by suppressing the expression of Bak1.	[40]
miR-130b	CSF-1	The low expression of miR-130b reduce the efficiency in binding to CSF-1 3’UTR, thereby reducing the sensitivity of ovarian cancer cells to cisplatin and paclitaxel.	[41]
miR-141	YAP1	The overexpression of miR-141 can suppress the resistance of esophageal squamous cell carcinoma (ESCC) to cisplatin which is mediated by YAP1 gene.	[42]
miR-143	KRAS	miR-143 could increase the drug-sensitivity of prostate cancer by suppressing the expression of target protein KRAS, while the overexpression of miR-143 could also participate the regulation of EGFR/RAS/MAPK pathway and improve the sensitivity of prostate cancer cells to docetaxel.	[43]
miR-146b-3p	K-ras	The increase of miR-146b-3p expression could participate the form of in resistance of HCT-116 colon cancer cell to cetuximab.	[44]
miR-193a	p73	The suppression of miR-193a expression caused by inhibiting p-73-mediated feedback regulatory pathway can induce the sensitivity of head and neck squamous cell JHU-029 to chemotherapeutic drugs.	[45]
miR-200c	PTEN Bax	miR-200c could reverse the resistance of the gastric cancer cells SGC7901 to DDP by upregulating the expression of the target protein PTEN/Bax.	[46]
miR-200bc/429	Bcl-2 XIAP	The enhanced expression of miR-200bc/429 cluster resulting decrease of BCL-2 and XIAP protein, which make the gastric SGC7901/VCR and lung cancer A549/CDDP became sensitive to VCR/CDDP induced apoptosis.	[47]
miR-205/31	BCL2 E2F6	miR-205/31 could suppress the expression of BCL2/E2F6 respectively, and improving the apoptosis of prostate cancer induced by chemotherapy. The downexpression of miR-205/miR-31 plays an important role in the anti-apoptotic function of tumor.	[48]
miR-297	MRP-2	In HCT116/L-OHP of the colon cancer cell with multi-drug resistant, the expression of miR-297 was significantly reduced when compared with the parental strain HCT116. Thereby overexpression of miR-297 is expected to improve the drug-resistant of HCT116/LOHP.	[49]
miR-328	BCRP ABCG2	In MCF-7/MX100 of the drug-resistant cell lines, suppress the expression of miR-328 could promote the expression of BCRP/ABCG2, which could increase drug sinotrans and result the generation of drug resistance.	[50]
miR-451	MDR1	In the multi-drug resistant cell lines MCF-7/DOX, overexpression of miR-451 may enhance the sensitivity of cells to doxorubicin.	[51]