# LncRNAs: key regulators and molecular mechanisms in lung cancer radiosensitivity

**Authors:** Yuhan Chen, Jiajie Shi, Changcheng Qin, Shuhua Yang, Burong Hu, Junfang Yan

PMC · DOI: 10.1515/med-2026-1379 · Open Medicine · 2026-03-06

## TL;DR

This paper reviews how long non-coding RNAs (lncRNAs) influence lung cancer radiosensitivity and could improve radiotherapy outcomes.

## Contribution

The paper provides a comprehensive review of lncRNA molecular mechanisms in lung cancer radiosensitivity and their potential as biomarkers and therapeutic targets.

## Key findings

- LncRNAs regulate DNA repair, apoptosis, and cell cycle in lung cancer radiosensitivity.
- They show potential as predictive biomarkers and therapeutic targets for precision radiotherapy.
- LncRNA-based strategies may overcome radioresistance in lung cancer treatment.

## Abstract

Lung cancer presents a major global public health challenge due to its high incidence and mortality rates, highlighting the urgent need for effective treatment strategies. Radiotherapy, a cornerstone in lung cancer treatment, faces significant limitations due to both intrinsic and acquired radioresistance in tumors. Recent researches have identified long non-coding RNAs (lncRNAs) as critical regulatory factors that significantly affect the radiosensitivity of lung cancer cells. These lncRNAs are involved in key biological processes, including DNA damage repair, apoptotic signaling, cell cycle progression, tumor microenvironment remodeling. This review comprehensively summarizes and discusses the molecular mechanisms by which lncRNAs influence radiosensitivity and assesses their potential as predictive biomarkers for radiotherapy. Additionally, it analyzes the potential of lncRNA-based intervention strategies to overcome radioresistance and enhance radiotherapy regimens. The goal is to provide a robust theoretical foundation for advancing precision radiotherapy in lung cancer. In summary, lncRNAs function as multidimensional regulators of lung cancer radiosensitivity and represent promising targets for radiosensitization in the precision medicine era.

## Linked entities

- **Diseases:** lung cancer (MONDO:0005138)

## Full-text entities

- **Genes:** LINC00857 (long intergenic non-protein coding RNA 857) [NCBI Gene 439990] {aka HUMT}, SFPQ (splicing factor proline and glutamine rich) [NCBI Gene 6421] {aka POMP100, PPP1R140, PSF}, CBR3-AS1 (CBR3 antisense RNA 1) [NCBI Gene 100506428] {aka PlncRNA-1, PlncRNA1}, MIR216B (microRNA 216b) [NCBI Gene 100126319] {aka MIRN216B, mir-216b}, LINC00662 (long intergenic non-protein coding RNA 662) [NCBI Gene 148189], XRCC5 (X-ray repair cross complementing 5) [NCBI Gene 7520] {aka KARP-1, KARP1, KU80, KUB2, Ku86, NFIV}, Atm (ataxia telangiectasia mutated) [NCBI Gene 11920] {aka C030026E19Rik}, CASC2 (cancer susceptibility 2) [NCBI Gene 255082] {aka C10orf5}, MIR296 (microRNA 296) [NCBI Gene 407022] {aka MIRN296, miRNA296, mir-296}, GNAS (GNAS complex locus) [NCBI Gene 2778] {aka AHO, AIMAH1, C20orf45, GNAS1, GPSA, GSA}, TAFAZZIN (tafazzin, phospholipid-lysophospholipid transacylase) [NCBI Gene 6901] {aka BTHS, CMD3A, EFE, EFE2, G4.5, LVNCX}, SERPINA3 (serpin family A member 3) [NCBI Gene 12] {aka AACT, ACT, GIG24, GIG25}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, ZNFX1 (zinc finger NFX1-type containing 1) [NCBI Gene 57169] {aka IMD91}, PDK1 (pyruvate dehydrogenase kinase 1) [NCBI Gene 5163], NEK2 (NIMA related kinase 2) [NCBI Gene 4751] {aka HsPK21, NEK2A, NLK1, PPP1R111, RP67}, CPS1 (carbamoyl-phosphate synthase 1) [NCBI Gene 1373] {aka CPS1D, CPSASE1, GATD6, PHN}, TCF7 (transcription factor 7) [NCBI Gene 6932] {aka TCF-1}, DDIT3 (DNA damage inducible transcript 3) [NCBI Gene 1649] {aka AltDDIT3, C/EBPzeta, CEBPZ, CHOP, CHOP-10, CHOP10}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 9451] {aka PEK, PERK, WRS}, LINC00323 (long intergenic non-protein coding RNA 323) [NCBI Gene 284835] {aka C21orf130, NCRNA00323, PRED42}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, SNHG4 (small nucleolar RNA host gene 4) [NCBI Gene 724102] {aka NCRNA00059, U19H}, PVT1 (Pvt1 oncogene) [NCBI Gene 5820] {aka LINC00079, MIR1204HG, NCRNA00079, TP53LC09, onco-lncRNA-100}, KDM3A (lysine demethylase 3A) [NCBI Gene 55818] {aka JHDM2A, JHMD2A, JMJD1, JMJD1A, TSGA}, AGAP2-AS1 (AGAP2 antisense RNA 1) [NCBI Gene 100130776] {aka PUNISHER}, LATS1 (large tumor suppressor kinase 1) [NCBI Gene 9113] {aka WARTS, wts}, CRYBG3 (crystallin beta-gamma domain containing 3) [NCBI Gene 131544] {aka DKFZp667G2110, vlAKAP}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, PARP1 (poly(ADP-ribose) polymerase 1) [NCBI Gene 142] {aka ADPRT, ADPRT 1, ADPRT1, ARTD1, PARP, PARP-1}, H19 (H19 imprinted maternally expressed transcript) [NCBI Gene 283120] {aka ASM, ASM1, BWS, D11S813E, GMRSP, LINC00008}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, SOX2-OT (SOX2 overlapping transcript) [NCBI Gene 347689] {aka NCRNA00043, SOX2OT}, ATR (ATR checkpoint kinase) [NCBI Gene 545] {aka FCTCS, FRP1, MEC1, SCKL, SCKL1}, YAP1 (Yes1 associated transcriptional regulator) [NCBI Gene 10413] {aka COB1, YAP, YAP-1, YAP2, YAP65, YKI}, SNHG1 (small nucleolar RNA host gene 1) [NCBI Gene 23642] {aka LINC00057, NCRNA00057, U22HG, UHG, lncRNA16}, RPTOR (regulatory associated protein of MTOR complex 1) [NCBI Gene 57521] {aka KOG1, Mip1}, LINC01614 (long intergenic non-protein coding RNA 1614) [NCBI Gene 105373869] {aka LCAL4}, STING1 (stimulator of interferon response cGAMP interactor 1) [NCBI Gene 340061] {aka ERIS, MITA, MPYS, NET23, SAVI, STING}, JTB (jumping translocation breakpoint) [NCBI Gene 10899] {aka HJTB, HSPC222, PAR, hJT}, GAS5 (growth arrest specific 5) [NCBI Gene 60674] {aka NCRNA00030, SNHG2}, ANXA2 (annexin A2) [NCBI Gene 302] {aka ANX2, ANX2L4, CAL1H, HEL-S-270, LIP2, LPC2}, FTX (FTX transcript, XIST regulator) [NCBI Gene 100302692] {aka LINC00182, MIR374AHG, NCRNA00182}, MALAT1 (metastasis associated lung adenocarcinoma transcript 1) [NCBI Gene 378938] {aka HCN, LINC00047, NCRNA00047, NEAT2, PRO2853, miPEP-52}, MIRLET7E (microRNA let-7e) [NCBI Gene 406887] {aka LET7E, MIRNLET7E, hsa-let-7e, let-7e}, HOTAIRM1 (HOXA transcript antisense RNA, myeloid-specific 1) [NCBI Gene 100506311] {aka HOXA-AS1, HOXA1-AS1, NCRNA00179}, LOC401317 [NCBI Gene 401317], DANCR (differentiation antagonizing non-protein coding RNA) [NCBI Gene 57291] {aka AGU2, ANCR, KIAA0114, SNHG13, lncRNA-ANCR}, MAGI2-AS3 (MAGI2 antisense RNA 3) [NCBI Gene 100505881], EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit) [NCBI Gene 2146] {aka ENX-1, ENX1, EZH2b, KMT6, KMT6A, WVS}, NIPSNAP1 (nipsnap homolog 1) [NCBI Gene 8508], FAM201A (family with sequence similarity 201 member A) [NCBI Gene 158228] {aka C9orf122}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, HNRNPD (heterogeneous nuclear ribonucleoprotein D) [NCBI Gene 3184] {aka AUF1, AUF1A, HNRPD, P37, hnRNPD0}, HCG11 (HLA complex group 11) [NCBI Gene 493812] {aka CTA-14H9.3, bK14H9.3}, NEAT1 (nuclear paraspeckle assembly transcript 1) [NCBI Gene 283131] {aka LINC00084, NCRNA00084, TP53LC15, TncRNA, VINC}, PRKDC (protein kinase, DNA-activated, catalytic subunit) [NCBI Gene 5591] {aka DNA-PKC, DNA-PKcs, DNAPK, DNAPKc, DNPK1, HYRC}, NOTCH2 (notch receptor 2) [NCBI Gene 4853] {aka AGS2, HJCYS, hN2}, CGAS (cyclic GMP-AMP synthase) [NCBI Gene 115004] {aka C6orf150, D4, MB21D1, h-cGAS}
- **Diseases:** Cancer (MESH:D009369), diabetes (MESH:D003920), Lung cancer (MESH:D008175), pancreatic cancer (MESH:D010190), cervical cancer (MESH:D002583), Hypoxia (MESH:D000860), NSCLC (MESH:D002289), carcinogenesis (MESH:D063646), HR deficiencies (MESH:C535296), hypoxic (MESH:D002534), lung adenocarcinoma (MESH:D000077192), gastric cancer (MESH:D013274), cardiovascular disease (MESH:D002318), colorectal cancer (MESH:D015179), carcinogenic (MESH:D011230), metastasis (MESH:D009362), nasopharyngeal carcinoma (MESH:D000077274), esophageal cancer (MESH:D004938), necrosis (MESH:D009336), hepatocellular carcinoma (MESH:D006528), breast cancer (MESH:D001943)
- **Chemicals:** ADP (MESH:D000244), oxygen (MESH:D010100), ADP-ribose (MESH:D000246), N6-methyladenosine (MESH:C010223), copper (MESH:D003300), Sorafenib (MESH:D000077157), micropeptides (MESH:C000722334), SSB (-), ribose (MESH:D012266), Olaparib (MESH:C531550), Niraparib (MESH:C545685), glutamine (MESH:D005973), m6A (MESH:C005955)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), NCI-H2170 — Homo sapiens (Human), Lung squamous cell carcinoma, Cancer cell line (CVCL_1535)

## Full text

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## Figures

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## References

129 references — full list in the complete paper: https://tomesphere.com/paper/PMC12962785/full.md

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Source: https://tomesphere.com/paper/PMC12962785