# Functional significance of miR-218 in lung cancer

**Authors:** Divyanshu Aggarwal, Anita Thyagarajan, Ravi P. Sahu

PMC · DOI: 10.20517/2394-4722.2025.108 · Journal of cancer metastasis and treatment · 2026-04-01

## TL;DR

This review explores how miR-218, a microRNA, acts as a tumor suppressor in lung cancer by regulating key cancer-related pathways and its potential as a diagnostic and therapeutic tool.

## Contribution

The paper consolidates experimental and clinical evidence on miR-218's role in lung cancer, highlighting its translational significance as a biomarker and therapeutic target.

## Key findings

- miR-218 regulates cell signaling pathways involved in cancer progression, such as proliferation and metastasis.
- Clinical evidence shows lower miR-218 levels correlate with increased tumor aggressiveness in lung cancer.
- miR-218 is being explored as a potential diagnostic biomarker and therapeutic target for lung cancer.

## Abstract

Lung cancer remains one of the most prevalent and lethal malignancies worldwide, characterized by a poor prognosis and high mortality rates. Although therapeutic strategies targeting oncogenic signaling cascades, such as receptor tyrosine kinases, have shown promising outcomes by regulating cellular functions such as survival and proliferation, their long-term effectiveness is often limited by mechanisms, including tumor resistance, drug toxicity, and adverse events. These challenges underscore the urgent need to identify new molecular targets and develop alternative therapeutic approaches. One promising avenue lies in the exploration of microRNAs (miRs) and their significance in cancer biology. Among them, miR-218 has drawn significant attention for its tumor-suppressive properties. Multiple experimental studies have emphasized the role of miR-218 as a key regulator of cell signaling pathways critical to cancer progression, including proliferation, invasion, metastasis, and apoptosis. Notably, miR-218 has been investigated as both a diagnostic biomarker and a therapeutic target. Importantly, clinical evidence further supports its relevance, showing an inverse correlation between miR-218 expression levels and tumor aggressiveness, reinforcing its translational significance. This review logically consolidates the functional significance, mechanistic insights, and experimental and clinical findings that emphasize the pivotal role of miR-218 in regulating molecular pathways involved in lung cancer growth.

## Linked entities

- **Genes:** Mir218 (microRNA 218) [NCBI Gene 387214]
- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** Alk (ALK receptor tyrosine kinase) [NCBI Gene 266802], Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, PTPRA (protein tyrosine phosphatase receptor type A) [NCBI Gene 5786] {aka HEPTP, HLPR, HPTPA, HPTPalpha, LRP, PTPA}, SNHG12 (small nucleolar RNA host gene 12) [NCBI Gene 85028] {aka ASLNC04080, C1orf79, LINC00100, LINC001000, NCRNA00100, PNAS-123}, SLIT2 (slit guidance ligand 2) [NCBI Gene 9353] {aka SLIL3, Slit-2}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, ERO1A (endoplasmic reticulum oxidoreductase 1 alpha) [NCBI Gene 30001] {aka ERO1-L, ERO1-L-alpha, ERO1-alpha, ERO1L, ERO1LA, Ero1alpha}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, CDK4 (cyclin dependent kinase 4) [NCBI Gene 1019] {aka CMM3, MCPH31, PSK-J3}, Snai2 (snail family zinc finger 2) [NCBI Gene 20583] {aka Slug, Slugh, Snail2}, VIM (vimentin) [NCBI Gene 7431], CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, ZEB2 (zinc finger E-box binding homeobox 2) [NCBI Gene 9839] {aka HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, BMI1 (BMI1 proto-oncogene, polycomb ring finger) [NCBI Gene 648] {aka FLVI2/BMI1, PCGF4, RNF51, flvi-2/bmi-1}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, VOPP1 (VOPP1 WW domain binding protein) [NCBI Gene 81552] {aka ECOP, GASP, WBP1L2}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, SNAI2 (snail family transcriptional repressor 2) [NCBI Gene 6591] {aka SLUG, SLUGH, SLUGH1, SNAIL2, WS2D}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, G6PD (glucose-6-phosphate dehydrogenase) [NCBI Gene 2539] {aka CNSHA1, G6PD1}, Slit2 (slit guidance ligand 2) [NCBI Gene 20563] {aka Drad-1, E030015M03Rik, E130320P19Rik, Slil3, b2b1200.1Clo, mKIAA4141}, LINC00173 (long intergenic non-protein coding RNA 173) [NCBI Gene 100287569] {aka NCRNA00173}, Shmt1 (serine hydroxymethyltransferase 1 (soluble)) [NCBI Gene 20425] {aka Shmt, cSHMT, mshmt, mshmt1, mshmt2}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, MIR218-2 (microRNA 218-2) [NCBI Gene 407001] {aka MIRN218-2, mir-218-2}, MCL1 (MCL1 apoptosis regulator, BCL2 family member) [NCBI Gene 4170] {aka BCL2L3, EAT, MCL1-ES, MCL1L, MCL1S, Mcl-1}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, SHMT1 (serine hydroxymethyltransferase 1) [NCBI Gene 6470] {aka CSHMT, SHMT, hcSHMT}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, TRIM9 (tripartite motif containing 9) [NCBI Gene 114088] {aka RNF91, SPRING}, MIR218-1 (microRNA 218-1) [NCBI Gene 407000] {aka MIRN218-1, mir-218-1}, Mki67 (antigen identified by monoclonal antibody Ki 67) [NCBI Gene 17345] {aka D630048A14Rik, Ki-67, Ki67}, Ptpra (protein tyrosine phosphatase receptor type A) [NCBI Gene 19262] {aka Ptpa, Ptpalpha, Rptpalpha, Rptra, Rptralpha}, Egfr (epidermal growth factor receptor) [NCBI Gene 24329] {aka ERBB1, ErbB-1, Errp}, DROSHA (drosha ribonuclease III) [NCBI Gene 29102] {aka ETOHI2, HSA242976, RANSE3L, RN3, RNASE3L, RNASEN}, CSK (C-terminal Src kinase) [NCBI Gene 1445], HS3ST3B1 (heparan sulfate-glucosamine 3-sulfotransferase 3B1) [NCBI Gene 9953] {aka 3-OST-3B, 3OST3B1, h3-OST-3B}, PXN (paxillin) [NCBI Gene 5829], ADAM9 (ADAM metallopeptidase domain 9) [NCBI Gene 8754] {aka CORD9, MCMP, MDC9, Mltng}, PRKDC (protein kinase, DNA-activated, catalytic subunit) [NCBI Gene 5591] {aka DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, HK2 (hexokinase 2) [NCBI Gene 3099] {aka HKII, HXK2}, SLIT3 (slit guidance ligand 3) [NCBI Gene 6586] {aka MEGF5, SLIL2, SLIT1, Slit-3, slit2}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, PFKM (phosphofructokinase, muscle) [NCBI Gene 5213] {aka ATP-PFK, GSD7, PFK-1, PFK-A, PFK1, PFKA}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, Mir218 (microRNA 218) [NCBI Gene 387214] {aka Mirn218}, CDCP1 (CUB domain containing protein 1) [NCBI Gene 64866] {aka CD318, SIMA135, TRASK}, CCAT1 (colon cancer associated transcript 1) [NCBI Gene 100507056] {aka CARLO5, CARLo-5, onco-lncRNA-40}
- **Diseases:** lung tumor metastasis (MESH:D009362), MECHANISMS (MESH:D041781), leukemias (MESH:D007938), Lung cancer (MESH:D008175), carcinogenesis (MESH:D063646), Adenocarcinoma (MESH:D000230), SCLC (MESH:D055752), colorectal cancer (MESH:D015179), immunodeficient (MESH:D007153), AC (MESH:D055577), NSCLC (MESH:D002289), toxicity (MESH:D064420), tumorigenic (MESH:D002471), cervical cancer (MESH:D002583), LCC (MESH:D018287), SCID (MESH:D016511), Cancer Metastasis (MESH:D009369), thyroid cancer (MESH:D013964), LUAD (MESH:D000077192), retinoblastoma (MESH:D012175), LUSC (MESH:D002294), T- and B-cell deficiencies (MESH:D016393), inflammatory (MESH:D007249), TNM (MESH:D008207), breast cancer (MESH:D001943), sarcomatoid carcinoma (MESH:D002292)
- **Chemicals:** oxygen (MESH:D010100), carbon (MESH:D002244), lactate (MESH:D019344), heparan sulfate (MESH:D006497), serine (MESH:D012694), DDP (-), Nicotinamide Adenine Dinucleotide Phosphate (MESH:D009249), pentose phosphate (MESH:D010428), cisplatin (MESH:D002945), platinum (MESH:D010984), radon (MESH:D011886), gefitinib (MESH:D000077156), taxane (MESH:C080625), folate (MESH:D005492), doxycycline (MESH:D004318), Glucose (MESH:D005947), carboplatin (MESH:D016190)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Nicotiana tabacum (American tobacco, species) [taxon 4097]
- **Mutations:** Y789F, A549R
- **Cell lines:** Calu-1 — Homo sapiens (Human), Lung squamous cell carcinoma, Cancer cell line (CVCL_0608), H358 — Homo sapiens (Human), Minimally invasive lung adenocarcinoma, Cancer cell line (CVCL_1559), LUAD — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_WN45), H1435 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1470), PC-9 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_B260), F4 — Mus musculus (Mouse), Mouse erythroid leukemia, Cancer cell line (CVCL_9R58), H1975 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1511), PC9GR — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_DI29), BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), CALU6 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0236), HCC827 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_2063), SPCA-1 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_6955), H661 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_1577), CL1-0 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_3871), BM7 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_A5BS), H1793 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1496), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), CL1-5 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_D521), H2228 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1543), Ch27 — Homo sapiens (Human), Chondrosarcoma, Cancer cell line (CVCL_M602), 95D — Homo sapiens (Human), Lung giant cell carcinoma, Cancer cell line (CVCL_7110), H1299 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0060), HCC4006 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1269), H460 — Homo sapiens (Human), Lung large cell carcinoma, Cancer cell line (CVCL_0459), Calu-3 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0609), HCC827GR — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_V621), /c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103), NK-92 — Homo sapiens (Human), Natural killer cell lymphoblastic leukemia/lymphoma, Cancer cell line (CVCL_2142), XWLC — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_IQ71), H23 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1547)

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## References

132 references — full list in the complete paper: https://tomesphere.com/paper/PMC13038310/full.md

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Source: https://tomesphere.com/paper/PMC13038310