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Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin

  • Authors:
    • Ningning Fan
    • Guanying Liang
    • Jiayue Shao
    • Qi Wang
    • Lu Fu
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China, Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150001, P.R. China, Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150086, P.R. China, Department of Pathology, Shenzhen Yantian District People's Hospital, Shenzhen, Guangdong 518000, P.R. China
    Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 291
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    Published online on: May 13, 2026
       https://doi.org/10.3892/ol.2026.15646
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Abstract

Musculoaponeurotic fibrosarcoma oncogene homolog K (MAFK) and amphiregulin (AREG) promote non‑small cell lung cancer (NSCLC) progression. However, whether MAFK regulates AREG to mediate the escape of NSCLC cells from doxorubicin (DOX)‑induced senescence remains unclear. In the present study, chemotherapy‑modulated senescence‑related genes were identified through bioinformatics analysis. Human non‑small cell lung adenocarcinoma cell lines (A549 and PC‑9 cells) were treated with DOX to generate persistent A549 cells (PACs) and persistent PC‑9 cells (PPCs). The expression levels of MAFK, AREG and the senescence‑associated protein p21 wild‑type p53‑activated fragment 1 (p21waf1) were evaluated using western blotting and reverse transcription‑quantitative PCR. Senescence‑associated β‑galactosidase staining and colony formation assays were performed to assess cellular senescence and proliferation. The proportions of senescent and proliferating PACs and PPCs were quantified using flow cytometry. A chromatin‑immunoprecipitation assay was performed to examine the regulatory association between MAFK and AREG. AREG was associated with cellular senescence, as demonstrated by changes in senescence markers. In A549 and PC‑9 cells, DOX treatment upregulated p21waf1 expression, induced senescence, inhibited proliferation and downregulated both MAFK and AREG expression. By contrast, PACs/PPCs exhibited enhanced proliferation alongside elevated MAFK and AREG levels. PACs and PPCs comprised 60‑70% senescent cells and 30‑40% proliferating cells. MAFK bound directly to the AREG promoter region. In addition, MAFK overexpression reversed the suppressive effect of AREG knockdown on the proliferation of A549 and PC‑9 cells. Collectively, MAFK enabled NSCLC cells to escape DOX‑induced senescence by upregulating AREG and facilitated cell proliferation upon DOX treatment.
View Figures

Figure 1

Identification of senescence-related
DEGs. (A) Volcano plot of DEGs from the GSE dataset. (B) Venn
diagram showing the intersection between senescence-related genes
from the Aging Atlas database and DEGs from the GSE dataset. DEG,
differentially expressed gene; FC, fold-change; AREG, amphiregulin;
GSE, Gene expression omnibus series.

Figure 2

KEGG pathway enrichment analysis. (A)
Top 10 enriched KEGG pathways (excluding disease-related terms).
(B) KEGG terms demonstrating enrichment of AREG. (C) Chord diagram
visualizing the association between the AREG gene and enriched KEGG
pathways. KEGG, Kyoto Encyclopedia of Genes and Genomes; AREG,
amphiregulin.

Figure 3

DOX induces senescence and suppresses
proliferation of NSCLC cells, while enhancing proliferation of
persistent cells. (A) Western blot analysis of senescence-related
protein p21waf1 levels in (B) A549 and (C) PC-9 cells following DOX
treatment for 4 days. The effect of DOX treatment for 4 days in (D)
A549 and (E) PC-9 cell senescence was detected by SA
β-galactosidase staining. Scale bar, 50 µm. Magnification, ×200.
Expression of the SASP-related factors IL-6 and IL-8 was analyzed
by RT-qPCR: (F) IL-6 in A549 cells, (G) IL-8 in A549 cells, (H)
IL-6 in PC-9 cells and (I) IL-8 in PC-9 cells. The proliferation of
DOX-treated (J) A549 and (K) PC-9 cells and PACs/PPCs was assessed
by colony formation assay. **P<0.01 and ***P<0.001 vs.
control. DOX, doxorubicin; NSCLC, non-small cell lung cancer;
HSC70, heat-shock cognate protein 70; PAC, persistent A549 cell;
PPC, persistent PC-9 cell; p21waf1, p21 wild-type p53-activated
fragment 1; SA, senescence-associated.

Figure 4

Senescent cells constitute the
majority of persistent cells and DOX suppresses MAFK and AREG
expression in NSCLC cells but enhances expression in persistent
cells. (A-C) Emerging cells (PACs/PPCs) were analyzed by flow
cytometry following Ki67 staining. Cells were gated based on low
(green) or high (red) FSC/SSC values and Ki67 expression was
analyzed for each population. The PAC/PPC population was
heterogeneous and composed of ~60–70% senescent cells named PAS/PPS
cells and 30–40% of proliferating cells named PAD/PPD cells. (D and
E) Emerging cells were sorted by flow cytometry according to low
(PAD/PPD) or high (PAS/PPS) FSC/SSC values and SA-β-gal activity
was analyzed. Scale bar, 50 µm. Magnification, ×200. (F-I) MAFK and
AREG expression in PACs/PPCs was examined by RT-qPCR. (J-M) MAFK
and AREG expression in DOX-treated A549 and PC-9 cells and
PACs/PPCs was examined by RT-qPCR and GAPDH was used as an internal
standard. (N and O) Transfection efficiency of shAREG in emerging
A549 and PC-9 cells was examined using western blotting.
**P<0.01 and ***P<0.001 vs. control; ##P<0.01
and ###P<0.001 vs. shNC; ^^^P<0.001 vs.
PAD; &&&P<0.001 vs. PPD. DOX,
doxorubicin; MAFK, musculoaponeurotic fibrosarcoma oncogene homolog
K; AREG, amphiregulin; NSCLC, non-small cell lung cancer, PAC/PPC,
persistent A549/PC-9 cells; FSC/SSC, forward-scatter/side-scatter;
PAS/PPS, persistent A549/PC-9 senescent; PAD/PPD, persistent
A549/PC-9 dividing; SA-β-gal, senescence-associated
β-galactosidase; RT-qPCR, reverse transcription-quantitative PCR;
HSC70, heat-shock cognate protein 70; sh, short hairpin; NC,
negative control.

Figure 5

AREG knockdown suppresses
proliferation and promotes senescence of NSCLC cells. The
proliferation of emerging (A) A549 and (B) PC-9 cells following
AREG knockdown was evaluated by colony formation assay. Emerging
cells (PACs/PPCs) were analyzed by flow cytometry following Ki67
staining: (C) Representative Ki67 staining plots in A549 cells, (D)
representative Ki67 staining plots in PC-9 cells, (E)
quantification of Ki67-positive A549 PAC subpopulations (PAD and
PAS), and (F) quantification of Ki67-positive PC-9 PPC
subpopulations (PPD and PPS). Cells were gated into two populations
based on low (green) or high (red) FSC/SSC values and Ki67
expression was analyzed for each population. Emerging (G) A549 and
(H) PC-9 cells were sorted by flow cytometry according to low
(PAD/PPD) or high (PAS/PPS) FSC/SSC values and
senescence-associated β-galactosidase activity was analyzed. Scale
bar, 50 µm. Magnification, ×200. ###P<0.001 vs. shNC;
^^^P<0.001 vs. PAD;
&&&P<0.001 vs. PPD. MAFK,
musculoaponeurotic fibrosarcoma oncogene homolog K; AREG,
amphiregulin; NSCLC, non-small cell lung cancer; PAC/PPC,
persistent A549 or PC-9 cells; FSC/SSC,
forward-scatter/side-scatter; PAS/PPS, persistent A549 or PC-9
senescent; PAD/PPD, persistent A549 or PC-9 dividing; sh, short
hairpin; NC, negative control.

Figure 6

MAFK overexpression reverses the
inhibitory effect of AREG knockdown on proliferation of emerging
NSCLC cells. The association between MAFK and AREG in (A) A549 and
(B) PC-9 cells was identified using chromatin-immunoprecipitation.
(C) Western blotting was used to examine the transfection
efficiency of plasmids overexpressing MAFK in (D) A549 and (E) PC-9
cells. AREG promoter activity in (F) A549 and (G) PC-9 cells was
detected by dual luciferase assay. The proliferation of emerging
(H) A549 and (I) PC-9 cells after MAFK overexpression and/or AREG
knockdown was assessed using colony formation assay. **P<0.01
and ***P<0.001 vs. control; +++P<0.001 vs. NC.
MAFK, musculoaponeurotic fibrosarcoma oncogene homolog K; AREG,
amphiregulin; NSCLC, non-small cell lung cancer; HSC70: heat-shock
cognate protein 70; sh, short hairpin; NC, negative control; MUT,
mutant; WT, wild-type; DOX, doxorubicin.
View References

1 

Lu X, Kang N, Ling X, Pan M, Du W and Gao S: MiR-27a-3p promotes non-small cell lung cancer through SLC7A11-mediated-ferroptosis. Front Oncol. 11:7593462021. View Article : Google Scholar : PubMed/NCBI

2 

Gu G, Hu C, Hui K, Zhang H, Chen T, Zhang X and Jiang X: Exosomal miR-136-5p derived from anlotinib-resistant NSCLC cells confers anlotinib resistance in non-small cell lung cancer through targeting PPP2R2A. Int J Nanomedicine. 16:6329–6343. 2021. View Article : Google Scholar : PubMed/NCBI

3 

Liang L, Hui K, Hu C, Wen Y, Yang S, Zhu P, Wang L, Xia Y, Qiao Y, Sun W, et al: Autophagy inhibition potentiates the anti-angiogenic property of multikinase inhibitor anlotinib through JAK2/STAT3/VEGFA signaling in non-small cell lung cancer cells. J Exp Clin Cancer Res. 38:712019. View Article : Google Scholar : PubMed/NCBI

4 

Le Duff M, Gouju J, Jonchère B, Guillon J, Toutain B, Boissard A, Henry C, Guette C, Lelièvre E and Coqueret O: Regulation of senescence escape by the cdk4-EZH2-AP2M1 pathway in response to chemotherapy. Cell Death Dis. 9:1992018. View Article : Google Scholar : PubMed/NCBI

5 

Sharpless NE and Sherr CJ: Forging a signature of in vivo senescence. Nat Rev Cancer. 15:397–408. 2015. View Article : Google Scholar : PubMed/NCBI

6 

Bolitho C, Moscova M, Baxter RC and Marsh DJ: Amphiregulin increases migration and proliferation of epithelial ovarian cancer cells by inducing its own expression via PI3-kinase signaling. Mol Cell Endocrinol. 533:1113382021. View Article : Google Scholar : PubMed/NCBI

7 

Wang L, Wang L, Zhang H, Lu J, Zhang Z, Wu H and Liang Z: AREG mediates the epithelial-mesenchymal transition in pancreatic cancer cells via the EGFR/ERK/NF-κB signalling pathway. Oncol Rep. 43:1558–1568. 2020.PubMed/NCBI

8 

Tu CY, Wang BW, Cheng FJ, Chen CH, Hsia TC, Wei YL, Chen CY, Hsieh IS, Yeh YL, Wang LY, et al: Incense burning smoke sensitizes lung cancer cells to EGFR TKI by inducing AREG expression. Am J Cancer Res. 8:2575–2589. 2018.PubMed/NCBI

9 

Fujino M, Tagami A, Ojima M, Mizuno S, Abdellatif AM, Kuno A and Takahashi S: c-MAF deletion in adult C57BL/6J mice induces cataract formation and abnormal differentiation of lens fiber cells. Exp Anim. 69:242–249. 2020. View Article : Google Scholar : PubMed/NCBI

10 

Hong E, Yik J, Amanatullah DF, Di Cesare PE and Haudenschild DR: c-Maf transcription factor regulates ADAMTS-12 expression in human chondrogenic cells. Cartilage. 4:177–186. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Wang R, Zheng J, Zhang DS, Yang YH and Zhao ZF: Wnt1-induced MAFK expression promotes osteosarcoma cell proliferation. Genet Mol Res. 14:7315–7325. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Sakurai T, Isogaya K, Sakai S, Morikawa M, Morishita Y, Ehata S, Miyazono K and Koinuma D: RNA-binding motif protein 47 inhibits Nrf2 activity to suppress tumor growth in lung adenocarcinoma. Oncogene. 35:5000–5009. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Malaquin N, Martinez A and Rodier F: Keeping the senescence secretome under control: Molecular reins on the senescence-associated secretory phenotype. Exp Gerontol. 82:39–49. 2016. View Article : Google Scholar : PubMed/NCBI

14 

Massrieh W, Derjuga A, Doualla-Bell F, Ku CY, Sanborn BM and Blank V: Regulation of the MAFF transcription factor by proinflammatory cytokines in myometrial cells. Biol Reprod. 74:699–705. 2006. View Article : Google Scholar : PubMed/NCBI

15 

Almeida GM, Duarte TL, Farmer PB, Steward WP and Jones GD: Multiple end-point analysis reveals cisplatin damage tolerance to be a chemoresistance mechanism in a NSCLC model: Implications for predictive testing. Int J Cancer. 122:1810–1819. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Mosieniak G, Sliwinska MA, Alster O, Strzeszewska A, Sunderland P, Piechota M, Was H and Sikora E: Polyploidy formation in doxorubicin-treated cancer cells can favor escape from senescence. Neoplasia. 17:882–893. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Zhang B, Shetti D, Fan C and Wei K: miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3. Biol Res. 52:382019. View Article : Google Scholar : PubMed/NCBI

18 

Vétillard A, Jonchère B, Moreau M, Toutain B, Henry C, Fontanel S, Bernard AC, Campone M, Guette C and Coqueret O: Akt inhibition improves irinotecan treatment and prevents cell emergence by switching the senescence response to apoptosis. Oncotarget. 6:43342–43362. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Jonchère B, Vétillard A, Toutain B, Lam D, Bernard AC, Henry C, De Carné Trécesson S, Gamelin E, Juin P, Guette C and Coqueret O: Irinotecan treatment and senescence failure promote the emergence of more transformed and invasive cells that depend on anti-apoptotic Mcl-1. Oncotarget. 6:409–426. 2015. View Article : Google Scholar : PubMed/NCBI

20 

Maarouf A, Boissard A, Henry C, Leman G, Coqueret O, Guette C and Lelièvre E: Anterior gradient protein 2 is a marker of tumor aggressiveness in breast cancer and favors chemotherapy-induced senescence escape. Int J Oncol. 60:52022. View Article : Google Scholar : PubMed/NCBI

21 

Olszewska A, Borkowska A, Granica M, Karolczak J, Zglinicki B, Kieda C and Was H: Escape from cisplatin-induced senescence of hypoxic lung cancer cells can be overcome by hydroxychloroquine. Front Oncol. 11:7383852022. View Article : Google Scholar : PubMed/NCBI

22 

Dragoj M, Milosevic Z, Bankovic J, Tanic N, Pesic M and Stankovic T: Targeting CXCR4 and FAK reverses doxorubicin resistance and suppresses invasion in non-small cell lung carcinoma. Cell Oncol (Dordr). 40:47–62. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Schmucker H, Blanding WM, Mook JM, Wade JF, Park JP, Kwist K, Shah H and Booth BW: Amphiregulin regulates proliferation and migration of HER2-positive breast cancer cells. Cell Oncol (Dordr). 41:159–168. 2018. View Article : Google Scholar : PubMed/NCBI

24 

Bormann F, Stinzing S, Tierling S, Morkel M, Markelova MR, Walter J, Weichert W, Roßner F, Kuhn N, Perner J, et al: Epigenetic regulation of Amphiregulin and Epiregulin in colorectal cancer. Int J Cancer. 144:569–581. 2019. View Article : Google Scholar : PubMed/NCBI

25 

Shimada H, Abe S, Kohno T, Satohisa S, Konno T, Takahashi S, Hatakeyama T, Arimoto C, Kakuki T, Kaneko Y, et al: Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer. Sci Rep. 7:370492017. View Article : Google Scholar : PubMed/NCBI

26 

Lee IN, Yang JT, Hsieh MJ, Huang C, Huang HC, Ku YJ, Wu YP, Huang KC and Chen JC: Knockdown of amphiregulin triggers doxorubicin-induced autophagic and apoptotic death by regulating endoplasmic reticulum stress in glioblastoma cells. J Mol Neurosci. 70:1461–1470. 2020. View Article : Google Scholar : PubMed/NCBI

27 

Chen JC, Huang C, Lee IN, Wu YP and Tang CH: Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway. Mol Carcinog. 57:1816–1824. 2018. View Article : Google Scholar : PubMed/NCBI

28 

Elangovan IM, Vaz M, Tamatam CR, Potteti HR, Reddy NM and Reddy SP: FOSL1 promotes kras-induced lung cancer through amphiregulin and cell survival gene regulation. Am J Respir Cell Mol Biol. 58:625–635. 2018. View Article : Google Scholar : PubMed/NCBI

29 

Hsu YL, Huang MS, Cheng DE, Hung JY, Yang CJ, Chou SH and Kuo PL: Lung tumor-associated dendritic cell-derived amphiregulin increased cancer progression. J Immunol. 187:1733–1744. 2011. View Article : Google Scholar : PubMed/NCBI

30 

Yuan W, Xu W, Li Y, Jiang W, Li Y, Huang Q, Chen B, Wu S, Wang Y, Song W, et al: TAZ sensitizes EGFR wild-type non-small-cell lung cancer to gefitinib by promoting amphiregulin transcription. Cell Death Dis. 10:2832019. View Article : Google Scholar : PubMed/NCBI

31 

Taniguchi H, Takeuchi S, Fukuda K, Nakagawa T, Arai S, Nanjo S, Yamada T, Yamaguchi H, Mukae H and Yano S: Amphiregulin triggered epidermal growth factor receptor activation confers in vivo crizotinib-resistance of EML4-ALK lung cancer and circumvention by epidermal growth factor receptor inhibitors. Cancer Sci. 108:53–60. 2017. View Article : Google Scholar : PubMed/NCBI

32 

Mitry MA, Laurent D, Keith BL, Sira E, Eisenberg CA, Eisenberg LM, Joshi S, Gupte S and Edwards JG: Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity. Am J Physiol Cell Physiol. 318:C380–C391. 2020. View Article : Google Scholar : PubMed/NCBI

33 

Sharma A and Almasan A: Autophagy and PTEN in DNA damage-induced senescence. Adv Cancer Res. 150:249–284. 2021. View Article : Google Scholar : PubMed/NCBI

34 

Xu Q, Long Q, Zhu D, Fu D, Zhang B, Han L, Qian M, Guo J, Xu J, Cao L, et al: Targeting amphiregulin (AREG) derived from senescent stromal cells diminishes cancer resistance and averts programmed cell death 1 ligand (PD-L1)-mediated immunosuppression. Aging Cell. 18:e130272019. View Article : Google Scholar : PubMed/NCBI

35 

Kannan MB, Solovieva V and Blank V: The small MAF transcription factors MAFF, MAFG and MAFK: Current knowledge and perspectives. Biochim Biophys Acta. 1823:1841–1846. 2012. View Article : Google Scholar : PubMed/NCBI

36 

Okita Y, Kimura M, Xie R, Chen C, Shen LT, Kojima Y, Suzuki H, Muratani M, Saitoh M, Semba K, et al: The transcription factor MAFK induces EMT and malignant progression of triple-negative breast cancer cells through its target GPNMB. Sci Signal. 10:eaak93972017. View Article : Google Scholar : PubMed/NCBI

37 

Ikeda H, Nishi S and Sakai M: Transcription factor Nrf2/MafK regulates rat placental glutathione S-transferase gene during hepatocarcinogenesis. Biochem J. 380:515–521. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Nicolas A, Deplanche M, Commere PH, Diot A, Genthon C, Marques da Silva W, Azevedo V, Germon P, Jamme H, Guédon E, et al: Transcriptome architecture of osteoblastic cells infected with Staphylococcus aureus reveals strong inflammatory responses and signatures of metabolic and epigenetic dysregulation. Front Cell Infect Microbiol. 12:8542422022. View Article : Google Scholar : PubMed/NCBI

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Spandidos Publications style
Fan N, Liang G, Shao J, Wang Q and Fu L: Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin. Oncol Lett 32: 291, 2026.
APA
Fan, N., Liang, G., Shao, J., Wang, Q., & Fu, L. (2026). Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin. Oncology Letters, 32, 291. https://doi.org/10.3892/ol.2026.15646
MLA
Fan, N., Liang, G., Shao, J., Wang, Q., Fu, L."Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin". Oncology Letters 32.1 (2026): 291.
Chicago
Fan, N., Liang, G., Shao, J., Wang, Q., Fu, L."Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin". Oncology Letters 32, no. 1 (2026): 291. https://doi.org/10.3892/ol.2026.15646
Copy and paste a formatted citation
x
Spandidos Publications style
Fan N, Liang G, Shao J, Wang Q and Fu L: Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin. Oncol Lett 32: 291, 2026.
APA
Fan, N., Liang, G., Shao, J., Wang, Q., & Fu, L. (2026). Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin. Oncology Letters, 32, 291. https://doi.org/10.3892/ol.2026.15646
MLA
Fan, N., Liang, G., Shao, J., Wang, Q., Fu, L."Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin". Oncology Letters 32.1 (2026): 291.
Chicago
Fan, N., Liang, G., Shao, J., Wang, Q., Fu, L."Breaking senescence restriction: MAFK‑AREG axis promotes NSCLC cells to resist doxorubicin". Oncology Letters 32, no. 1 (2026): 291. https://doi.org/10.3892/ol.2026.15646
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