TABLE 3.
Specific miRNAs have been revealed to control the expression of amino acid transporters.
| Transporters | Endogenous substrates | miRNAs | Diseases and/or model systems | Findings | References |
|---|---|---|---|---|---|
| SLC1A1/EAAT3 | L-glutamic acid L-aspartic acid L-cysteine | miR-26a-5p | 20 clinical multiple sclerosis samples Oligodendrocyte hybrid cell line MO3-13 | Transfection of miR-26a in MO3-13 cells reduced SLC1A1 mRNA by 50% and protein 30%. In 20 patients with MS treated with INF-β, miR-26a levels were increased SLC1A1 mRNA was decreased | Potenza et al. (2018) |
| miR-183-5p, miR-96-5p, miR-182-5p | Light adaptation in mouse retina Mouse embryonic fibroblast NIH 3T3 cells C57BL/6 mice, Sprague-Dawley rats, and Wistar rats | miR-183/96/182 are upregulated in light-adapted mouse retinas and downregulated with dark adaptation Enhanced green fluorescent protein and firefly luciferase reporters to confirm miR-183/96/182 direct binding to SLC1A1 | Krol et al. (2010) | ||
| miR-96-5p | Multiple system atrophy Human cases from University of California San Diego Alzheimer Disease Research Center 5 transgenic mouse models (MBP1-hαsyn tg, MBP29-hαsyn tg, mThy1-hαsyn tg, mThy1-hAPP tg, mThy1-htau) and non-transgenic mice | Luciferase assay to confirm direct binding of miR-96 to SLC1A1 | Ubhi et al. (2014) | ||
| miR-96-5p | Neuroprotection against oxidative stress Neuroblastoma cell line SH-SY5Y and HEK293 cell line male ddY mice | Transfection with miR-96-5p downregulates SLC1A1 protein by about 40% | Kinoshita et al. (2014) | ||
| Rno-miR-101b-3p and hsa-miR-101-3p | Rat model of major depressive disorder (FSL and FRL) | Luciferase reporter assay was used to confirm the binding of miR-101 in HEK 293 cells. miR101-b was decreased, while SLC1A1 mRNA levels were increased in in FSL mice | Wei et al. (2016) | ||
| SLC1A2/EAAT2 | L-glutamic acid L-aspartic acid | miR-31-5p miR-200c-3p | Liver aging markers in liver transplants human liver biopsies HEK 293 cells | Transfection with miR-200c mimic reduced SLC1A2 mRNA by about 50%, while miR-31 mimic reduced SLC1A2 mRNA by over 90% | Capri et al. (2017) |
| SLC1A3/EAAT1/GLAST | L-glutamic acid L-aspartic acid | miR-155-5p | astrocytes in epilepsy Wistar rats | Luciferase reporter assay with transfection of miR-155-5p and SLC1A3 3′UTR vector resulted in about 60% decrease of luciferase activity | Gao et al. (2017) |
| SLC1A5/ASCT2 | L-alanine, L-serine, L-cysteine, L-threonine, L-glutamine, L-asparagine, etc. | miR-137-3p | Melanoma cell lines A375 and G-361 and xenograft mouse model | miR-137 overexpression reduced SLC1A5 mRNA by about 50% and protein by about 75% miR-137 inhibition increased SLC1A5 mRNA about 1.5-fold and protein 1.5–1.6-fold. Transfection with miR-137 reduces SLC1A5 and blocks ferroptosis | Luo et al. (2018) |
| miR-924-5p | Non-small-cell lung cancer cell lines NCI-H1299, HCC827, A549, H460, 16HBE cell lines and xenograft mouse model | Luciferase reporter assay with transfection of miR-924 and SLC1A5 3′UTR vector resulted in about 50% decrease of luciferase activity. Circ_0000463 is overexpressed in NSCLC and sponges miR-924 to prevent binding to SLC1A5 | Liu et al. (2022) | ||
| miR-149-5p | Breast cancer cell lines MDA-MB-231, BT-549, MCF-10A, and kidney cell line 293T 60 clinical paired breast cancer and normal tissue samples BALB/C nude mice | Luciferase reporter assay with transfection of miR-149-5p and SLC1A5 3′UTR vector resulted in about 60% decrease of luciferase activity. circular RNA septin 9 sponges miR-149-5p | Wang J. et al. (2021) | ||
| miR-107-3p | Esophageal carcinoma cell lines ECA109, KYSE410, KYSE150, TE1, and esophageal epithelial cell line HEEC 39 clinical paired esophageal cancer and normal tissue samples Male xenograft mouse model | miR-107 overexpression decreased SLC1A5 protein by about 50%, while miR-107 inhibition increased protein by about 2-fold Circ-SFMBT2 sponges miR-107 | Chang et al. (2021) | ||
| SLC7A1/CAT1 | L-arginine, L-lysine, L-ornithine, L-histidine | miR-122-5p | Hepatocyte cell lines Huh7, HepG2, AML-12, WC-3, and kidney cell line 293T mouse samples and human primary hepatocytes | Negative correlation between miR-122 and SLC7A1 in primary human hepatocytes, Huh7, HepG2, and 293T, but not in AML-12 | Chang et al. (2004) |
| Cellular stress HeLa, HEK293, HepG2, Huh7, and DLD-1 | miR-122 binds to SLC7A1 to repress translation, but HuR prevents repression during cellular stress | Bhattacharyya et al. (2006) | |||
| miR-145-5p | 10 male spontaneously hypertensive rats and 10 age-matched normotensive male Wistar-Kyoto rats | Inhibiting miR-145 resulted in about 2.5-fold increase in SLC7A1 mRNA | Wang and Jin, (2018) | ||
| SLC7A5/LAT1 | Neutral AAs | miR-126-3p | Small cell lung cancer cell lines H69 and HTB-172 Primary small cell lung cancer samples | miR-126 overexpression reduced SLC7A5 mRNA more than 50% | Miko et al. (2011), Li H. et al. (2018) |
| Gastric cancer cell lines SGC-7901, MKN-45, MKN-28, GES-1 cell lines 54 matched primary gastric cancer and noncancerous tissue samples | miR-126 expression downregulated SLC7A5 by about 50% | Wang et al., (2015) | |||
| 80 paired lung cancer and non-tumor samples Lung cancer cell lines A549, H226, H1299, and H446, and lung epithelial cell line BESA-2B | miR-126 inhibition increases SLC7A5 expression PVT1-5 sponges miR-126 to prevent SLC7A5 repression | Li H. et al. (2018) | |||
| miR-193a-3p | XB130 effect on cancer cells WRO and MRO cells | miR-193a mimic reduced SCL7A5 protein levels by about 50% XB130 suppresses miR-193a | Takeshita et al. (2013) | ||
| miR-6775-3p | Esophageal squamous cell carcinoma cell lines TE1, Eca109, Ec9706, and KYSE30 138 clinical esophageal squamous cell carcinoma clinical samples Xenograft tumor mouse model | In TE1 cells transfected with miR-6775-3p mimics, SLC7A5 was decreased by about 70%. In Ec9706 cells transfected with miR-6775-3p inhibitor, SLC7A5 was increased by about 2.5-fold | Meng et al. (2018) | ||
| miR-328-3p | Human osteosarcoma 143B and MG63 cells | MiR-328-3p reduced SLC7A5 3′UTR luciferase reporter activities and protein outcomes but did not alter the overall homeostasis of AAs. Combination treatment with miR-328 plus cisplatin or doxorubicin synergistically inhibited osteosarcoma cell proliferation | Yi et al. (2020) | ||
| miR-199b-5p | Endometrial adenocarcinoma cell lines HEC1A, Ishikawa, and hEEC 46 clinical endometrial cancer and 46 healthy tissue samples xenograft mouse model GSE115810 and GSE36389 datasets | Transfection with miR-199b-5p mimics decreased SLC7A5 protein by about 50% | Shu et al. (2021) | ||
| miR-138-5p | Retinoblastoma cell lines WERI-RB-1, Y79, HXO-RB44, SO-RB50, and rectal adenocarcinoma cell line HRA, 33 retinoblastoma samples and 21 normal samples Mouse tumor model | Transfection with miR-138-5p reduced SLC7A5 protein by about 50% circ-FAM158A sponges SLC7A5 | Zheng et al. (2021) | ||
| SLC7A11/xCT | Cystine and glutamate | miR-26b-5p | Breast cancer cell lines MCF7, HCC 1937, MDA-MB-231, and CCD-1095Sk | miR-26b overexpression reduces SLC7A11 protein, while miR-26b inhibitors increase SLC7A11 protein | Liu et al. (2011) |
| miR-27a-3p | cisplatin resistance in bladder cancer Bladder cancer cell lines EJ/T24 and RT112 354 clinical bladder cancer samples | Transfection of cisplatin-resistant cells with pre-miR precursor to miRNA-27a decreased SLC7A11 protein and increased cisplatin sensitivity 100-fold | Drayton et al. (2014) | ||
| Lung cancer cell line A549 and lung epithelial cell line Beas-2B GSE27262, GSE102287, GSE116959, GSE118370, and GSE19945 datasets 90 clinical paired NSCLC and normal tissue samples | Non-small-cell lung cancer Transfection with miR-27a-3p mimic reduced SLC7A11 expression by about 50% | Lu et al. (2021) | |||
| miR-139-5p | Pancreatic carcinoma cell lines PANC-1, Bx-PC3, and HPDE TCGA-PAAD database 45 paired pancreatic carcinoma and normal tissue samples Xenograft mouse model | Transfection with miR-139-5p mimics reduced SLC7A11 mRNA by about 50% | Zhu et al. (2020) | ||
| miR-375-3p | Oral squamous cell carcinoma cell lines Fadu, SCC-25, CAL-27, Tca8113, and Hs 680.Tg 40 clinical oral squamous cell carcinoma and paired normal samples | Transfection with miR-375 mimics reduces SLC7A11 by about 60% | Wu et al. (2017) | ||
| miR-378a-3p | ferroptosis in I/R-induced renal injury Human kidney cell lines HK-2 and TCMK-1 I/R-induced kidney injury rats | miR-378a-3p mimic transfection does not have a significant impact on SLC7A11 mRNA but does reduce SLC7A11 protein by about 60% | Ding et al. (2020) | ||
| miR-557-3p | Pancreatic cancer cell lines HPDE, Hs 766T, and SW1990 93 clinical paired pancreatic cancer and normal samples Xenograft mouse model | Transfection with miR-557 mimic reduced SLC7A11 protein by about 60% | Zhang T. et al. (2021) | ||
| miR-876-5p | Oral squamous cell carcinoma cell lines Cal-27, SCC9, HOK, and kidney cell line 293T 34 oral squamous cell carcinoma tissues and 19 non-tumor samples male BALB/c nude mice | Transfecting cells with miR-876-5p inhibitor increases SLC7A11 by about 1.5-2-fold. CircCDR1 acted as an oncogene by sponging miR-876-5p | Cui et al. (Online ahead of print) | ||
| miR-382-5p | Lidocaine-induced ferroptosis in ovarian and breast cancer Ovarian adenocarcinoma cell line SKOV-3 and breast cancer cell line T47D 38 clinical ovarian cancer samples and 50 clinical breast cancer samples Xenograft model with male mice | Transfection with miR-382-5p mimic reduces SLC7A11 mRNA by about 75% | Sun et al. (2021) | ||
| miR-1261-5p | Hepatocellular carcinoma cell lines HepG2, BEL-7402, MHCC-97H, and hepatocyte cell line LO2 Female mouse xenograft model | Transfection with miR-1261 mimic reduced SLC7A11 expression by about 40–50% circ0097009 acts as a sponge for miR-1261 | Lyu et al. (2021) | ||
| SLC25A12 | Aspartate Glutamate | miR-302b-3p | MAVS-mediated antiviral innate immunity HEK293, HeLa, A549, MRC-5, HAP-1 cell lines | Transfection with miR-302b mimics reduced SLC25A12 by about 50% | Yasukawa et al. (2020) |
| SLC38A1/SNAT1 | Neutral AAs | miR-593-3p | Insulin-promoted glucose consumption Hepatoma cell lines HepG2, BeL7402, and mouse myoblast cell line C2C12 41 paired liver cancer and normal samples Primary human hepatocyte cultures | Transfection with miR-593-3p mimics reduced SLC38A1 protein by about 60% and miR-593-3p inhibitor increased protein level by about 3-fold | Yang et al. (2016) |
| MiR-138-5p | Colorectal cancer cell lines SW480 and SW620, normal colon cell line HCoEpiC 30 paired clinical colorectal cancer and normal samples Xenograft mouse model | Transfection with miR-138 reduces SLC38A1 mRNA by about 50%, while SLC38A1 protein is reduced by about 60% in SW480 cells and 50% in SW620 cells. The long noncoding RNA NEAT1 sponges miR-138 | Wang S. et al. (2021) | ||
| miR-150-5p | Pulmonary fibrosis Lung fibroblast cell line HFL1 Male Sprague-Dawley rats | Transfection with miR-150-5p mimic downregulated SLC38A1 by about 50%. lncRNA ZFAS1 sponges miR-150-5p | Yang et al. (2020) | ||
| miR-511-3p | Hepatocellular carcinoma cell lines HepG2, Huh7, and L-02 TCGA data | Inhibition of miR-511 increases SLC38A1 mRNA by about 50% and increases protein by about 1.5–2-fold. LINC01559 sponges miR-511 | Su and Wang, (2021) | ||
| miR-485-5p | Colorectal cancer cell lines SW480, and SW620, and NCM460 31 paired clinical colorectal cancer and normal samples Male xenograft mouse model | Transfection with miR-485-5p decreased SLC38A1 protein by about 50%, while miR-485-5p inhibition increased protein by about 3-fold. CircRUNX1 sponges miR-485-5p | Yu et al. (2021) |