Skip to main content

Advertisement

SpringerLink
Log in

Small molecules with huge impacts: the role of miRNA-regulated PI3K pathway in human malignancies

  • Review
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Along with evolution, a considerable number of signaling cascades have evolved within cells to meet their multifaceted needs. Among transmitting molecules, phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR) have teamed up to build a signaling axis that effectively regulates various cellular processes including cell proliferation and migration. Given the extensive output of the PI3K/Akt/mTOR signaling axis, its aberrancy could subsequently lead to the formation of a wide range of human cancers spanning from hematologic malignancies to different types of solid tumors. Despite the high frequency of the PI3K pathway over-activation in most malignancies, mutations in the DNA sequence are not equally common. Such incompatibility sheds light on the possible effects of post-translational modification mechanisms that may take control of this pathway, some of the most important ones of which are through microRNAs (miRNAs or miRs). The present review is designed to take off the veil from the regulatory role of these small non-coding RNAs on the PI3K/Akt/mTOR signaling axis in carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Not applicable.

Code availability

Not applicable.

Abbreviations

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

APL:

Acute promyelocytic leukemia

BC:

Bladder cancer

BrC:

Breast cancer

CLL:

Chronic lymphoid leukemia

CML:

Chronic myeloid leukemia

CRC:

Colorectal cancer

CREB:

CAMP-response element binding protein

DLBCL:

Diffuse large B-cell lymphoma

EC:

Endometrial cancer

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-mesenchymal transition

FOXO1:

Forkhead box protein O1

GC:

Gastric cancer

GPCRs:

G protein-coupled receptors

GSK-3B:

Glycogen-synthesis kinase-3B

HCC:

Hepatocellular carcinoma

HER2:

Human epidermal growth factor receptor 2

HM:

Hematologic malignancies

HNSCC:

Head and neck squamous carcinoma

KRAS:

Kirsten rat sarcoma

MAPK:

Mitogen-activated protein kinase

MDM2:

Mouse double minute 2 homolog

miR:

MicroRNA

miRNA:

MicroRNA

miRISC:

MiRNA-induced silencing complex

MM:

Multiple myeloma

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor kappa B

NSCLS:

Non-small cell lung cancer

OC:

Ovarian cancer

PC:

Prostate cancer

PDAC:

Pancreatic ductal adenocarcinoma

PDCD4:

Programmed cell death 4 protein

PI3K:

Phosphoinositide 3-kinase

PIP2:

Phosphatidylinositol-4,5-diphosphate

PKB:

Protein kinase B

PTEN:

Phosphatase and tensin homolog

RNAi:

RNA interference

RTKs:

Tyrosine kinase receptors

TSC2:

Tuberous sclerosis complex 2

UTR:

Untranslated region

VEGF:

Vascular endothelial growth factor

References

  1. Osaki M, Oshimura M, Ito H (2004) PI3K-Akt pathway: its functions and alterations in human cancer. Apoptosis 9(6):667–676

    CAS  PubMed  Google Scholar 

  2. Soung YH et al (2006) Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas. Oncology 70(4):285–289

    CAS  PubMed  Google Scholar 

  3. Goh JN et al (2016) microRNAs in breast cancer: regulatory roles governing the hallmarks of cancer. Biol Rev 91(2):409–428

    PubMed  Google Scholar 

  4. Svoronos AA, Engelman DM, Slack FJ (2016) OncomiR or tumor suppressor? The duplicity of microRNAs in cancer. Cancer Res 76(13):3666–3670

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Hu M et al (2019) MicroRNAs and the PTEN/PI3K/Akt pathway in gastric cancer. Oncol Rep 41(3):1439–1454

    CAS  PubMed  Google Scholar 

  6. Noorolyai S et al (2019) The relation between PI3K/AKT signalling pathway and cancer. Gene 698:120–128

    CAS  PubMed  Google Scholar 

  7. Porta C, Paglino C, Mosca A (2014) Targeting PI3K/Akt/mTOR signaling in cancer. Front Oncol 4:64

    PubMed  PubMed Central  Google Scholar 

  8. Carnero A et al (2008) The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 8(3):187–198

    CAS  PubMed  Google Scholar 

  9. Vara JÁF et al (2004) PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 30(2):193–204

    CAS  Google Scholar 

  10. Milella M et al (2015) PTEN: multiple functions in human malignant tumors. Front Oncol 5:24

    PubMed  PubMed Central  Google Scholar 

  11. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    CAS  PubMed  Google Scholar 

  12. Purow B (2009) MicroRNAs in the central nervous system and potential roles of RNA interference in brain tumors. CNS cancer. Humana Press, Totowa, pp 651–677

    Google Scholar 

  13. Lewis BP et al (2003) Prediction of mammalian microRNA targets. Cell 115(7):787–798

    CAS  PubMed  Google Scholar 

  14. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11(9):597–610

    CAS  PubMed  Google Scholar 

  15. Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19(6):586–593

    CAS  PubMed  Google Scholar 

  16. Santhekadur PK et al (2012) Multifunction protein staphylococcal nuclease domain containing 1 (SND1) promotes tumor angiogenesis in human hepatocellular carcinoma through novel pathway that involves nuclear factor κB and miR-221. J Biol Chem 287(17):13952–13958

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Yoo BK et al (2011) Increased RNA-induced silencing complex (RISC) activity contributes to hepatocellular carcinoma. Hepatology 53(5):1538–1548

    CAS  PubMed  Google Scholar 

  18. Pink RC et al (2011) Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 17(5):792–798

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kashani B et al (2019) You are what you eat: Sequence analysis reveals how plant microRNAs may regulate the human genome. Comput Biol Med 106:106–113

    CAS  PubMed  Google Scholar 

  20. Chakraborty C, Sharma AR, Sharma G (2020) Therapeutic advances of miRNAs: a preclinical and clinical update. J Adv Res 28:127–138

    PubMed  PubMed Central  Google Scholar 

  21. Park S et al (2010) Role of the PI3K/AKT and mTOR signaling pathways in acute myeloid leukemia. Haematologica 95(5):819–828

    CAS  PubMed  Google Scholar 

  22. Bertacchini J et al (2015) Targeting PI3K/AKT/mTOR network for treatment of leukemia. Cell Mol Life Sci 72(12):2337–2347

    CAS  PubMed  Google Scholar 

  23. Jia CY et al (2011) MiR-223 suppresses cell proliferation by targeting IGF-1R. PloS One 6(11):e27008

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen L et al (2019) microRNA-628 inhibits the proliferation of acute myeloid leukemia cells by directly targeting IGF-1R. Onco Targets Ther 12:907

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhou J-D et al (2019) MicroRNA-335/ID4 dysregulation predicts clinical outcome and facilitates leukemogenesis by activating PI3K/Akt signaling pathway in acute myeloid leukemia. Aging (Albany NY) 11(10):3376

    CAS  Google Scholar 

  26. Li Y et al (2013) Epigenetic silencing of microRNA-193a contributes to leukemogenesis in t (8; 21) acute myeloid leukemia by activating the PTEN/PI3K signal pathway. Blood J Am Soc Hematol 121(3):499–509

    CAS  Google Scholar 

  27. Bai H et al (2011) Involvement of miR-21 in resistance to daunorubicin by regulating PTEN expression in the leukaemia K562 cell line. FEBS Lett 585(2):402–408

    CAS  PubMed  Google Scholar 

  28. Li Z, Luo J (2018) Epigenetic regulation of HOTAIR in advanced chronic myeloid leukemia. Cancer Manage Res 10:5349

    CAS  Google Scholar 

  29. Palacios F et al (2015) Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation. Leukemia 29(1):115–125

    CAS  PubMed  Google Scholar 

  30. Olive V et al (2009) miR-19 is a key oncogenic component of mir-17-92. Genes Dev 23(24):2839–2849

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Go H et al (2015) MicroRNA-21 plays an oncogenic role by targeting FOXO1 and activating the PI3K/AKT pathway in diffuse large B-cell lymphoma. Oncotarget 6(17):15035

    PubMed  PubMed Central  Google Scholar 

  32. Han B, Wang S, Zhao H (2020) MicroRNA-21 and microRNA-155 promote the progression of Burkitt’s lymphoma by the PI3K/AKT signaling pathway. Int J Clin Exp Pathol 13(1):89

    PubMed  PubMed Central  Google Scholar 

  33. Roccaro AM et al (2009) MicroRNAs 15a and 16 regulate tumor proliferation in multiple myeloma. Blood J Am Soc Hematol 113(26):6669–6680

    CAS  Google Scholar 

  34. Jiang Y, Chang H, Chen G (2018) Effects of microRNA-20a on the proliferation, migration and apoptosis of multiple myeloma via the PTEN/PI3K/AKT signaling pathway. Oncol Lett 15(6):10001–10007

    PubMed  PubMed Central  Google Scholar 

  35. Tokunaga E et al (2006) Activation of PI3K/Akt signaling and hormone resistance in breast cancer. Breast Cancer 13(2):137–144

    PubMed  Google Scholar 

  36. Rask L et al (2011) High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer. APMIS 119(10):663–673

    PubMed  Google Scholar 

  37. Li N et al (2017) MiR-106b and miR-93 regulate cell progression by suppression of PTEN via PI3K/Akt pathway in breast cancer. Cell Death Dis 8(5):e2796–e2796

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang LF et al (2020) MicroRNA-425-5p promotes breast cancer cell growth by inducing PI3K/AKT signaling. Kaohsiung J Med Sci 36(4):250–256

    CAS  PubMed  Google Scholar 

  39. Bahena-Ocampo I et al (2016) miR-10b expression in breast cancer stem cells supports self-renewal through negative PTEN regulation and sustained AKT activation. EMBO Rep 17(5):648–658

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Li C et al (2018) miR-19b serves as a prognostic biomarker of breast cancer and promotes tumor progression through PI3K/AKT signaling pathway. Onco Targets Ther 11:4087

    PubMed  PubMed Central  Google Scholar 

  41. Gong C et al (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286(21):19127–19137

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Rahmani F et al (2020) Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer. Gene 737:144459

    CAS  PubMed  Google Scholar 

  43. Zhang Y et al (2019) Downregulation of microRNA-1469 promotes the development of breast cancer via targeting HOXA1 and activating PTEN/PI3K/AKT and Wnt/β-catenin pathways. J Cell Biochem 120(4):5097–5107

    CAS  PubMed  Google Scholar 

  44. Cui W et al (2013) micro RNA-133a regulates the cell cycle and proliferation of breast cancer cells by targeting epidermal growth factor receptor through the EGFR/A kt signaling pathway. FEBS J 280(16):3962–3974

    CAS  PubMed  Google Scholar 

  45. Zhu N et al (2011) Endothelial-specific intron-derived miR-126 is down-regulated in human breast cancer and targets both VEGFA and PIK3R2. Mol Cell Biochem 351(1–2):157–164

    CAS  PubMed  Google Scholar 

  46. Chen Y et al (2013) miRNA-200c increases the sensitivity of breast cancer cells to doxorubicin through the suppression of E-cadherin-mediated PTEN/Akt signaling. Mol Med Rep 7(5):1579–1584

    CAS  PubMed  Google Scholar 

  47. Network CGAR (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474(7353):609

    Google Scholar 

  48. Dobbin ZC, Landen CN (2013) The importance of the PI3K/AKT/MTOR pathway in the progression of ovarian cancer. Int J Mol Sci 14(4):8213–8227

    PubMed  PubMed Central  Google Scholar 

  49. Kuznetsov VA, Tang Z, Ivshina AV (2017) Identification of common oncogenic and early developmental pathways in the ovarian carcinomas controlling by distinct prognostically significant microRNA subsets. BMC Genomics 18(6):692

    PubMed  PubMed Central  Google Scholar 

  50. Polytarchou C et al (2011) Akt2 regulates all Akt isoforms and promotes resistance to hypoxia through induction of miR-21 upon oxygen deprivation. Cancer Res 71(13):4720–4731

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wang YQ et al (2013) MicroRNA-182 promotes cell growth, invasion, and chemoresistance by targeting programmed cell death 4 (PDCD4) in human ovarian carcinomas. J Cell Biochem 114(7):1464–1473

    CAS  PubMed  Google Scholar 

  52. Ghafouri-Fard S, Shoorei H, Taheri M (2020) miRNA profile in ovarian cancer. Exp Mol Pathol 113:104381

    CAS  PubMed  Google Scholar 

  53. Zhu L et al (2019) miR-494-3p promotes the progression of endometrial cancer by regulating the PTEN/PI3K/AKT pathway. Mol Med Rep 19(1):581–588

    CAS  PubMed  Google Scholar 

  54. Myatt SS et al (2010) Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res 70(1):367–377

    CAS  PubMed  Google Scholar 

  55. Imam JS et al (2012) Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PloS One 7(12):e52397

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Xiang Y et al (2014) MiR-152 and miR-185 co-contribute to ovarian cancer cells cisplatin sensitivity by targeting DNMT1 directly: a novel epigenetic therapy independent of decitabine. Oncogene 33(3):378–386

    CAS  PubMed  Google Scholar 

  57. Yu T et al (2018) Functions and mechanisms of microRNA-31 in human cancers. Biomed Pharmacother 108:1162–1169

    CAS  PubMed  Google Scholar 

  58. Li C et al (2019) MicroRNA-936 targets FGF2 to inhibit epithelial ovarian cancer aggressiveness by deactivating the PI3K/Akt pathway. Onco Targets Ther 12:5311

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Li Y et al (2016) A dual PI3K/AKT/mTOR signaling inhibitor miR-99a suppresses endometrial carcinoma. Am J Transl Res 8(2):719

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Kent C, Reed IG (2016) Regulation of epithelial–mesenchymal transition in endometrial cancer: connecting PI3K, estrogen signaling, and microRNAs. Clin Transl Oncol 18(11):1056–1061

    CAS  PubMed  Google Scholar 

  61. Liang M et al (2015) Downregulation of miR203 induces overexpression of PIK3CA and predicts poor prognosis of gastric cancer patients. Drug Des Dev Ther 9:3607

    CAS  Google Scholar 

  62. Tsukamoto Y et al (2010) MicroRNA-375 is downregulated in gastric carcinomas and regulates cell survival by targeting PDK1 and 14-3-3ζ. Cancer Res 70(6):2339–2349

    CAS  PubMed  Google Scholar 

  63. Zhang H et al (2015) MicroRNA-29s could target AKT2 to inhibit gastric cancer cells invasion ability. Med Oncol 32(1):342

    CAS  PubMed  Google Scholar 

  64. Xu M et al (2017) MicroRNA-379 inhibits metastasis and epithelial-mesenchymal transition via targeting FAK/AKT signaling in gastric cancer. Int J Oncol 51(3):867–876

    CAS  PubMed  Google Scholar 

  65. Wu L et al (2015) MicroRNA-137 contributes to dampened tumorigenesis in human gastric cancer by targeting AKT2. PloS One 10(6):e0130124

    PubMed  PubMed Central  Google Scholar 

  66. Chun-zhi Z et al (2010) MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer 10(1):1–10

    Google Scholar 

  67. Guo B et al (2014) miR-338-3p suppresses gastric cancer progression through a PTEN-AKT axis by targeting P-REX2a. Mol Cancer Res 12(3):313–321

    CAS  PubMed  Google Scholar 

  68. Eto K et al (2014) The microRNA-21/PTEN pathway regulates the sensitivity of HER2-positive gastric cancer cells to trastuzumab. Ann Surg Oncol 21(1):343–350

    PubMed  Google Scholar 

  69. Danielsen SA et al (2015) Portrait of the PI3K/AKT pathway in colorectal cancer. Biochim Biophys Acta (BBA) 1855(1):104–121

    CAS  Google Scholar 

  70. Reid JF et al (2012) miRNA profiling in colorectal cancer highlights miR-1 involvement in MET-dependent proliferation. Mol Cancer Res 10(4):504–515

    CAS  PubMed  Google Scholar 

  71. Guo S et al (2013) MicroRNA-497 targets insulin-like growth factor 1 receptor and has a tumour suppressive role in human colorectal cancer. Oncogene 32(15):1910–1920

    CAS  PubMed  Google Scholar 

  72. Guo C et al (2008) The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosom Cancer 47(11):939–946

    CAS  PubMed  Google Scholar 

  73. Diosdado B et al (2009) MiR-17-92 cluster is associated with 13q gain and c-myc expression during colorectal adenoma to adenocarcinoma progression. Br J Cancer 101(4):707–714

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Sarver AL, Li L, Subramanian S (2010) MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res 70(23):9570–9580

    CAS  PubMed  Google Scholar 

  75. Wu Y et al (2017) MicroRNA-21 (Mir-21) promotes cell growth and invasion by repressing tumor suppressor PTEN in colorectal cancer. Cell Physiol Biochem 43(3):945–958

    CAS  PubMed  Google Scholar 

  76. Park J-K et al (2009) Antisense inhibition of microRNA-21 or-221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas 38(7):e190–e199

    CAS  PubMed  Google Scholar 

  77. Liu J et al (2014) LPS induced miR-181a promotes pancreatic cancer cell migration via targeting PTEN and MAP2K4. Dig Dis Sci 59(7):1452–1460

    CAS  PubMed  Google Scholar 

  78. Sarkar S et al (2013) Down-regulation of miR-221 inhibits proliferation of pancreatic cancer cells through up-regulation of PTEN, p27kip1, p57kip2, and PUMA. Am J Cancer Res 3(5):465

    PubMed  PubMed Central  Google Scholar 

  79. Yonemori K et al (2017) MicroRNA in pancreatic cancer. J Hum Genet 62(1):33–40

    CAS  PubMed  Google Scholar 

  80. Fu X et al (2018) Exosomal microRNA-32-5p induces multidrug resistance in hepatocellular carcinoma via the PI3K/Akt pathway. J Exp Clin Cancer Res 37(1):52

    PubMed  PubMed Central  Google Scholar 

  81. Ohta K et al (2015) MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepatocellular carcinoma by directly inhibiting PTEN and CDKN1A. Oncotarget 6(5):3211

    PubMed  Google Scholar 

  82. Zhou Y et al (2017) Effect of microRNA-135a on cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer. Cell Physiol Biochem 42(4):1431–1446

    CAS  PubMed  Google Scholar 

  83. Xia H, Li Y, Lv X (2016) MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer. Int J Oncol 49(4):1325–1333

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhang J-G et al (2010) MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC). Clin Chim Acta 411(11–12):846–852

    CAS  PubMed  Google Scholar 

  85. Edmonds MD et al (2016) MicroRNA-31 initiates lung tumorigenesis and promotes mutant KRAS-driven lung cancer. J Clin Investig 126(1):349–364

    PubMed  Google Scholar 

  86. da Silva HB et al (2013) Dissecting major signaling pathways throughout the development of prostate cancer. Prostate Cancer 2013:1–23

    Google Scholar 

  87. Lee K-H et al (2009) MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation. Oncogene 28(38):3360–3370

    CAS  PubMed  Google Scholar 

  88. Ottley E, Gold E (2014) microRNA and non-canonical TGF-β signalling: Implications for prostate cancer therapy. Crit Rev Oncol Hematol 92(1):49–60

    PubMed  Google Scholar 

  89. Taheri M et al (2020) Expression profile of microRNAs in bladder cancer and their application as biomarkers. Biomed Pharmacother 131:110703

    CAS  PubMed  Google Scholar 

  90. Ding Z-S et al (2019) MicroRNA-34a inhibits bladder cancer cell migration and invasion, and upregulates PTEN expression. Oncol Lett 18(5):5549–5554

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Ashrafizadeh M et al (2020) PTEN: what we know of the function and regulation of this onco-suppressor factor in bladder cancer? Eur J Pharmacol 881:173226

    CAS  PubMed  Google Scholar 

  92. Enokida H et al (2016) The role of microRNAs in bladder cancer. Investig Clin Urol 57(Suppl 1):S60–S76

    PubMed  PubMed Central  Google Scholar 

  93. Yao Y et al (2014) MiR-330-mediated regulation of SH3GL2 expression enhances malignant behaviors of glioblastoma stem cells by activating ERK and PI3K/AKT signaling pathways. PloS One 9(4):e95060

    PubMed  PubMed Central  Google Scholar 

  94. Kefas B et al (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68(10):3566–3572

    CAS  PubMed  Google Scholar 

  95. Chen G et al (2010) MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2. Oncol Rep 23(4):997–1003

    CAS  PubMed  Google Scholar 

  96. He L et al (2019) Wnt/β-catenin signaling cascade: a promising target for glioma therapy. J Cell Physiol 234(3):2217–2228

    CAS  PubMed  Google Scholar 

  97. Vahabi M et al (2019) miR-96-5p targets PTEN expression affecting radio-chemosensitivity of HNSCC cells. J Exp Clin Cancer Res 38(1):1–16

    Google Scholar 

  98. Li T et al (2019) Long non-coding RNA HOTAIR/microRNA-206 sponge regulates STC2 and further influences cell biological functions in head and neck squamous cell carcinoma. Cell Prolif 52(5):e12651

    PubMed  PubMed Central  Google Scholar 

  99. Moradi N et al (2020) Emerging role of miR-372 and miR-101a in head and neck squamous cell carcinoma. Clin Lab. https://doi.org/10.7754/Clin.Lab.2019.190734

    Article  PubMed  Google Scholar 

  100. Lin P-C et al (2013) Epigenetic repression of miR-31 disrupts androgen receptor homeostasis and contributes to prostate cancer progression. Cancer Res 73(3):1232–1244

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to express their gratitude to Shahid Beheshti University of Medical Sciences (Tehran, Iran) for supporting this study.

Funding

None.

Author information

Author notes

  1. Bahareh Kashani and Zahra Zandi have contributed equally to this work as first authors.

Authors and Affiliations

  1. Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Bahareh Kashani, Zahra Zandi & Seyed H. Ghaffari

  2. Department of Medical Oncology and Hematology, Iran University of Medical Sciences, Tehran, Iran

    Vahid Kaveh

  3. Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Atieh Pourbagheri-Sigaroodi & Davood Bashash

Authors
  1. Bahareh Kashani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zahra Zandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vahid Kaveh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Atieh Pourbagheri-Sigaroodi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed H. Ghaffari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Davood Bashash
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

BK: Data curation, writing—original draft preparation, reviewing and editing. ZZ: data curation, writing—original draft preparation, reviewing and editing. VK: writing-reviewing and editing. AP-S: data curation, writing—original draft preparation. SHG: writing-reviewing and editing. DB: conceptualization, writing-reviewing and editing, approved the published version.

Corresponding author

Correspondence to Davood Bashash.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

11033_2021_6739_MOESM1_ESM.jpg

Supplementary file1 Expression profile of miRNAs associated with the regulation of the PI3K/Akt pathway in different types of human cancers. Although some miRNAs seem to be uniquely identified in a specific malignancy, others are known to play a part in various cancers. Moreover, some miRNAs are up-regulated in a cancer while being down-regulated in another; which is indicative of a possible cancer-specific or target-specific roles of miRNAs. HM hematologic malignancies; BrC breast cancer; OC ovarian cancer; BC bladder cancer; EC endometrial cancer; GC gastric cancer; CRC colorectal cancer; PDAC pancreatic ductal adenocarcinoma; PC prostate cancer; HCC hepatocellular carcinoma; NSCLS non-small cell lung cancer; HNSCC head and neck squamous carcinoma (JPG 5200 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kashani, B., Zandi, Z., Kaveh, V. et al. Small molecules with huge impacts: the role of miRNA-regulated PI3K pathway in human malignancies. Mol Biol Rep 48, 8045–8059 (2021). https://doi.org/10.1007/s11033-021-06739-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-021-06739-6

Keywords

Search

Navigation