The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers
Abstract
:1. Introduction
2. AKT3-Derived circRNAs
3. AKT3 and miRNA/AKT3 Axes in Human Cancers
3.1. Breast Cancer
BC Model System | AKT3 or Akt3/Functions | AKT3 Targets | Ref. |
---|---|---|---|
K-RAS mutated MDA-MB-231 cells; xenografts | AKT3/cell proliferation↑, tumor growth↑, post-irradiation cell survival↑ | [21] | |
3475 subline of MDA-MB-231 cells (lung metastasis); MDA-MB-231 | AKT3/tumor growth↑, metastasis↑, apoptosis↓ | ERK, Bim, Bax | [45] |
MDA-MB-231; MDA-MB-468 and MCF10DCIS xenografts | AKT3/TNBC growth↑ | p27 | [46] |
ErbB2(+) BC cells, mammary tumor cells | AKT3/cell proliferation↑, tamoxifen sensitivity↓ | pErbB2/pErbB3, Foxo3a, ERα | [47] |
MMTV-ErbB2, MMTV-PyMT mice (Neu- and PyMT- driven mammary oncogenesis) | Akt3/no effect on tumorigenesis of mouse BC cells | [48] | |
PyMT mouse BC cells | Akt3/metastasis of mouse BC cells↓ | [49] | |
MDA-MB-231 BO cells; xenografts | AKT3/migration↓, invasion↓ bone metastasis↓ | HER2, DDR kinase | [50] |
IBC cells: SUM149 | AKT3/survival of IBC↑, no effect on invasion | [51] |
Tumor Tissue/Cell Lines | LncRNA or circRNA/Functions | MiRNAs in the miRNA/AKT3 Axis/Related Functions | Ref. |
---|---|---|---|
Breast Cancer (BC) | |||
BC tissues; MDA-MB-231, HUVECs | miR-29b/ angiogenesis↓ tumorigenesis↓ | [36] | |
Docetaxel resistance of BC MCF7, MDA-MB-231, docetaxel resistant cell lines: MCF7/DTX, MDA-MB-231/DTX | miR-145/ cell viability↓, colony formation↓, docetaxel sensitivity↑ | [53] | |
MCF10A, MCF10. AT1, MCF10.neoT, CF10. Ca1d, MCF10. Ca1h, MCF10. DCIS | miR-29c/ preneoplastic TNBC cell proliferation↓, colonization ability↓ | [54] | |
MDA-MB-231 | miR-181a-5p/ viability↓, migration↓, survival↓, Warburg effect↓ | [55] | |
BC tissues; BT-549, MCF-7, MDA-MB-453, MDA-MB-231 | miR-433/ cell proliferation↓, cell viability↓, apoptosis↑ | [56] | |
Drug-resistant and drug-sensitive BC tumor tissues; MCF-7, MDA-MB-231, MDA-MB-468, T47D | miR-489/ chemosensitivity↑, cell proliferation↓, invasion↓ | [57] | |
MCF-7, MDA-MB-231 | miR-3614-3p/ invasion↓, migration↓ | [58] | |
BC tissues; MDA-MB-231 | circWHSC1/ cell growth↑, proliferation↑, migration↑, invasion↑, glycolysis↑, apoptosis↓ | miR-212-5p | [60] |
HCC1937, BT549, MDA-MB-231, MCF-7, T47D, BT474 | RP11-480I12.5-004/ cell proliferation↑, colony formation↑, apoptosis↓ | miR-29c-3p | [59] |
Non-small-cell lung cancer (NSCLC) | |||
NSCLC tissues; cell lines: BEAS-2B, A549, HCC823, NCL-H23, NCL-H358 cells | miR-217/ cell proliferation↓, apoptosis↑ | [61] | |
NSCLC tissues; A549 | circulating miR-320a/ metastatic potential↓, apoptosis↑ | [62] | |
NSCLC tissues; NSCLC cell lines: CALU3, CALU6, A549, H1229, H1975 | circWHSC1/ colony formation↑, viability↑, metastasis↑, progression↑ | miR-296-3p | [63] |
NSCLC tissues; NSCLC cell lines: A549 and H460 | circ_0016760/proliferation↑, migration↑, apoptosis↓ | miR-646 | [64] |
NSCLC tissues; Cell lines: NCI-H1299, A549, H460, NCI-H2106, H1975 | circ_0000520/ cell growth↑, migration↑, invasion↑ | miR-1258 | [65] |
Hepatocellular carcinoma (HCC) | |||
HCC specimens; HCC cell lines: HepG2 | miR-122, miR-124/ function not validated | [66] | |
HCC tissue samples and cell lines: Huh-7, SNU-182, SNU-475, Hep3B2, HepG2 | miR-122/ cell growth↓, migration↓, apoptosis↑, | [67] | |
HCC-BCLC9 cell | miR-122/ cell proliferation↓, dormancy↑ | [68] | |
HCC specimens; HepG2, HuH7, SMMC-7721 | miR-144/ cell proliferation↓, migration↓, invasion↓ | [69] | |
HCC tissues of solitary large, nodular, and small HCC; HCC cell lines: SMMC7721, HepG2, HUH7, MHCC97-L, MHCC97-H, HCCLM3 | miR-424/ cell proliferation↓ | [70] | |
HCC specimens; HCC cell lines: QGY-7703, Huh7, BEL-7402, HepG2, Hep3B | miR-582-5p/ colony formation↓, cell proliferation↓ | [71] | |
HCC tissues; HCC cell lines: SNU-449, SNU-182, Huh7, LM3, Bel-7405, SK-hep1, Hep3B | LINC00680/stemness behavior↑, chemosensitivity↓ | miR-568 | [72] |
HCC specimens; HCC cell lines: HepG2, Hep3B, Huh-7, SNU398, NU449, SNU182, SNU475 | miR-519d/AKT3? miR-519d/ cell proliferation↑, migration↑, apoptosis↓ | [73] | |
Colorectal cancer (CRC) | |||
CRC cell lines: RKO, HCT116 | miR-124-3p.1/ proliferation↓, metastasis↓ | [74] | |
CRC tissues; CRC cell lines: SW480, HCT116, LOVO, SW620 | miR-384/ proliferation↓ | [75] | |
CRC tissues; CRC cell lines: Colo205, SW620, HCT116, HT29, LOVO, SW480 | LINC02163/proliferation↑, metastasis↑ | miR-511-3p | [76] |
CRC tissues; CRC cell lines: LOVO, PKO, SW480, HT29 | lncRNA DSCAM-AS1/proliferation↑, invasion↑, migration↑ | miR-384 | [77] |
Gastric carcinoma (GC) | |||
GC tissues; cell lines: SGC-7901, MKN45, BGC823 | miR-195/ apoptosis↑ | [78] | |
Gastric adenocarcinoma serum; cell line: MGC-803 | MALAT1/ apoptosis↓ | miR-181a-5p | [79] |
GC tissues; GC cell lines: MKN28, NCI-N87, AGS, KATOIII, RF1, RF48 | circNF1/cell proliferation↑ | miR-16 | [80] |
Cholangiocarcinoma (CCA) cell lines: HCCC-9810, RBE | circRNA CDR1a/proliferation↑, invasion↑ | miR-641 | [81] |
Pancreatic cancer (PC) tissues; cell line: PANC-1 | miR-489/proliferation↓, apoptosis↑ | [82] | |
Ovarian cancer (OC)/epithelial ovarian cancer (EOC) | |||
EOC tissues; cell lines: SKOV3, A2780, HO8910, 3AO | miR-29b/ Warburg effect↓, tumor growth↓ | [83] | |
OC cell lines: SKOV3, OVCAR3, cisplatin-resistant SKOV and OVCAR3 cells | miR-489/ survival↓, growth↓, apoptosis↑, sensitivity of cisplatin-resistant OC to cisplatin↑ | [84] | |
OC tissues; Cell lines: CaOV3, OVCAR3, SKOV3 | RHPN1-AS1/proliferation↑, migration↑, invasion↑ | miR-665 | [85] |
OC tissues; OC cell lines: SKOV-3, ES-2, OVCAR3, A2780, CAOV3 | lncRNA EMX2OS/proliferation↑, invasion↑, tumor growth ↑ | miR-654 | [86] |
Endometrial carcinoma (EC) | |||
EC tissues; EC cell line ECC1 | miR-582-5p/proliferation↓, apoptosis↑ | [87] | |
Endometrial adenocarcinoma cell line: Ishikawa (ISK) cells | lncCDKN2B-AS1/proliferation↑, invasion↑ | miR-424-5p | [88] |
EC tissues; EC cell lines: HEC1A, HEC1B, Ishikawa | LINC01224/ proliferation↑, apoptosis↓ | miR-485-5p | [89] |
Thyroid carcinoma (TC)/papillary thyroid carcinoma (PTC) | |||
TC tissues; cell lines: TPC-1, FTC-133, 8505C; primary PTC cells; | miR-145/ growth↓, metastasis↓ | [90] | |
PTC tissues; PTC cell line: K1 | miR-29a/ growth↓, apoptosis↑, metastasis↓ | [91] | |
TC tissues; PTC cell lines: 8505C, TPC-1, SW1736 | miR-217/ proliferation↓, migration↓, invasion↓ | [92] | |
PTC tissues; PTC cell lines: B-CPAP, KTC-1 | lncRNA n384546/progression↑, metastasis↑ | miR-145-5p | [93] |
TC tissues; TC cell lines: BCPAP, K1, H7H83, TPC-1 | circ_0000144/proliferation↑, migration↑, invasion↑ | miR-217 | [94] |
Nasopharyngeal carcinoma (NPC) | |||
NPC tissues; Human primary NPC cell | miR-424-5p/ proliferation↓, migration↓, apoptosis↑ | [95] | |
NPC tissues; NPC cell lines: C666-1, SUNE1, 5-8 F, HNE1, HNE2 | circTRAF3/proliferation↑, invasion↑, apoptosis↓ | miR-203a-3p | [96] |
Oral squamous cell carcinoma (OSCC) tissues; cell line: SCC-4, SCC-25, HN-6, CAL-27, TCA-83 | miR-16/ proliferation↓, apoptosis↑ | [97] | |
Glioblastoma multiforme (GBM) | |||
GBM cell lines: T98G, U87, A172, LN229, LN18 | miR-610/ proliferation↓, anchorage independent growth↓ | [98] | |
GBM cell lines: LN229, A172, U373, SHG44 | lncRNA, GAS5/proliferation↓, migration↓, invasion↓ | miR-424 | [99] |
Multiple myeloma (MM) | |||
Primary MM cells, MM cell lines: MM.1S, RPMI8226 | miR-15a, miR-16-1/ cell proliferation↓ | [100] | |
MM cell lines: OPM2, RPMI-8226; Endothelial cell: HUVECs | miR-29b/ endothelial cell proliferation↓, migration↓, tube formation↓ | [101] | |
MM tissues; cell lines: KM3, H929, MM1S, U266 cells | circ_0000142/proliferation↑, metastasis↑ | miR-610 | [102] |
MM tissues; cell lines: OPM-2, U266, KM3, U1996, H929 | lncRNA FEZF1-AS1/ proliferation↑, apoptosis↓ | miR-610 | [103] |
Osteosarcoma (OS) | |||
OS tissues; cell lines: HOS, MG-63, Saos-2, SW1353, U2OS | miR-1258/ proliferation↓ | [104] | |
OS tissues; OS cell lines: HOS, MG-63, SaOS-2, U2OS, | MALAT1/ glycolysis↑, proliferation↑, metastasis↑ | miR-485-3p | [105] |
Uveal melanoma (UM) tissues; UM cell line: OCM-1A | miR-224-5p/ proliferation↓, migration↓, invasion↓ | [106] | |
UM cell lines: OMM2.5, UM001, Mel285, Mel290; UM xenografts | miR-181a-5p/ proliferation↓, colony formation↓, apoptosis↑, tumor growth ↓ | [107] | |
NK/T cell lymphoma (NKTL) tissues; cell lines: KHYG-1, NK-92, HANK-1, SNK-1, SNK-6 | miR-150/ sensitivity of NKTL to radiation treatment↑ | [108] | |
Bladder cancer TCGA database | miR-195/ cell proliferation↓ | [109] | |
Wilms’ tumor tissues; cell lines: 17–94, WIT49 | miR-22-3p/ proliferation↓, invasion↓ | [110] |
3.2. Lung Cancer
3.3. Digestive/Gastrointestinal Cancers
3.4. Gynecologic Cancers
3.5. Thyroid Carcinoma and Head and Neck Cancers
3.6. Other Types of Human Cancer
4. Dysregulation of the Same miRNA/AKT3 Axis in Different Cancers
5. Perspectives and Therapeutic Applications
6. Conclusions
Author Contributions
Funding
Informed Consent Statement
Conflicts of Interest
Abbreviations
Abbreviation | Full Name |
3′-UTRs | 3′-untranslated region |
CCA | cholangiocarcinoma |
ccRCC | clear cell renal cell carcinoma |
ceRNA | competitive endogenous RNA |
circRNAs | circular RNAs |
CRC | colorectal cancer |
DDR | discoidin domain receptors |
EC | endometrial carcinoma |
EOC | epithelial ovarian cancer |
ERα | estrogen receptor alpha |
GAS5 | growth arrest-specific 5 |
GBM | glioblastoma multiforme |
GC | gastric cancer |
HCC | hepatocellular carcinoma |
HER2 | ErbB2 receptor tyrosine kinase 2 |
HK2 | hexokinase2 |
HUVEC | human umbilical vein endothelial cells |
IBC | inflammatory breast cancer |
lncRNAs | long non-coding RNAs |
MALAT-1 | metastasis-associated lung adenocarcinoma transcript 1 |
miRNA, miR- | microRNA |
MM | multiple myeloma |
ncRNAs | non-coding RNAs |
NKTL | NK/T cell lymphoma |
NPC | nasopharyngeal carcinoma |
NSCLC | non-small-cell lung cancer |
OC | ovarian cancer |
OS | osteosarcoma |
OSCC | oral squamous cell carcinoma |
PC | pancreatic cancer |
PD-L1 | programmed death-ligand 1 |
PTC | papillary thyroid carcinoma |
RCC | renal cell carcinoma |
TGFβ | transforming growth factor β |
TNBC | triple-negative breast cancer |
ULM | uterine leiomyomas |
UM | uveal melanoma |
UTR | untranslated region |
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Tumor Tissue/Cell Lines | CircAKT3/Functions | Targets | Ref. |
---|---|---|---|
Lung cancer tissues; cell lines: A549 and H1299 | hsa_circ_0000199/ glycolysis↑, cell growth↑, drug sensitivity↓ | miR-516b-5p, STAT3 | [37] |
GC tissues; cell lines: SGC7901, BGC823, CDDP-resistant SGC7901, CDDP-resistant BGC823 | hsa_circ_0000199/ DNA damage repair↑, cell survival↑ | miR-198 | [38] |
TNBC tissues; cell lines: MCF-10A, MDA-MB-231, MDA-MB-468, SK-BR-3 | hsa_circ_0000199/ chemo-tolerance↑, proliferation↑, migration↑, invasion↑ | miR-206, miR-613 | [39] |
ccRCC tissues; cell lines: OSRC-2, Caki-1, SN12-PM6, A498, SW839 | hsa_circ_0017252/ metastasis↓ | miR-296-3p | [40] |
GBM tissues; cell lines: U251, HS683, SW1783, U373, glioma-initiating cells | hsa_circ_0017250/ proliferation↓, invasiveness↓ | AKT | [41] |
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Yang, C.; Hardy, P. The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers. Cells 2023, 12, 2594. https://doi.org/10.3390/cells12222594
Yang C, Hardy P. The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers. Cells. 2023; 12(22):2594. https://doi.org/10.3390/cells12222594
Chicago/Turabian StyleYang, Chun, and Pierre Hardy. 2023. "The Multifunctional Nature of the MicroRNA/AKT3 Regulatory Axis in Human Cancers" Cells 12, no. 22: 2594. https://doi.org/10.3390/cells12222594