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Original Research

Open Access

VGLL4 inhibits stemness and cisplatin resistance in non-small cell lung cancer via the COL3A1/NF-κB pathway

  • Jijun Xue1
  • Qin Ma2,*,
  • Wenfeng Han1

1Department of Thoracic surgery, Sun Yat-sen University Cancer Center Gansu Hospital, 730050 Lanzhou, Gansu, China

2Department of Respiratory Oncology, Sun Yat-sen University Cancer Center Gansu Hospital, 730050 Lanzhou, Gansu, China

DOI: 10.22514/jomh.2024.101 Vol.20,Issue 6,June 2024 pp.129-135

Submitted: 11 April 2024 Accepted: 07 June 2024

Published: 30 June 2024

*Corresponding Author(s): Qin Ma E-mail:


Previous studies have confirmed that vestigial-like protein 4 (VGLL4) can inhibit the malignant progression of lung cancer cells. However, its impact on cisplatin resistance and stemness in lung cancer cells remains unclear. In this study, we established cisplatin-resistant cells and transfected them with VGLL4 overexpression plasmid and siRNA. Their 50% inhibitory concentration (IC50) values were determined via Cell Counting Kit-8 (CCK-8) assay, cell proliferation was assessed via clone formation assay, apoptosis rate was measured by flow cytometry, sphere formation was quantified, and protein expression of collagen type III alpha 1 (COL3A1) and p-p65/p65 was analyzed using Western blot. Our findings demonstrate that VGLL4 enhances the sensitivity of cisplatin-resistant cells to cisplatin, inhibits cell proliferation, and promotes apoptosis. Moreover, VGLL4 suppresses sphere formation and the expression of stemness markers Nanog and Oct4 in cisplatin-resistant cells. Mechanistically, VGLL4 regulates the nuclear transcription factor-κB (NF-κB) pathway through COL3A1, thereby influencing the sensitivity and stemness characteristics of cisplatin-resistant cells. In conclusion, this study shows that VGLL4 can augment treatment sensitivity and suppress stemness of cisplatin-resistant cells, thereby proposing a potential therapeutic target for cisplatin-resistant lung cancer.


Lung cancer; VGLL4; Cisplatin resistance; Stemenss; COL3A1; NF-κB

Cite and Share

Jijun Xue,Qin Ma,Wenfeng Han. VGLL4 inhibits stemness and cisplatin resistance in non-small cell lung cancer via the COL3A1/NF-κB pathway. Journal of Men's Health. 2024. 20(6);129-135.


[1] He L, Luo L, Zhu H, Yang H, Zhang Y, Wu H, et al. FEN1 promotes tumor progression and confers cisplatin resistance in non-small-cell lung cancer. Molecular Oncology. 2017; 11: 640–654.

[2] Konoshenko M, Lansukhay Y, Krasilnikov S, Laktionov P. MicroRNAs as predictors of lung-cancer resistance and sensitivity to cisplatin. International Journal of Molecular Sciences. 2022; 23: 7594.

[3] MacDonagh L, Gray SG, Breen E, Cuffe S, Finn SP, O’Byrne KJ, et al. BBI608 inhibits cancer stemness and reverses cisplatin resistance in NSCLC. Cancer Letters. 2018; 428: 117–126.

[4] Guo L, Mohanty A, Singhal S, Srivastava S, Nam A, Warden C, et al. Targeting ITGB4/SOX2-driven lung cancer stem cells using proteasome inhibitors. iScience. 2023; 26: 107302.

[5] Sun JC, Wang L, Zhu XH, Shen ML. Hsa_circ_0006427 suppresses multiplication, migration and invasion of non-small cell lung cancer cells through miR-346/VGLL4 pathway. Cell Journal. 2022; 24: 245–254.

[6] Mickle M, Adhikary G, Shrestha S, Xu W, Eckert RL. VGLL4 inhibits YAP1/TEAD signaling to suppress the epidermal squamous cell carcinoma cancer phenotype. Molecular Carcinogenesis. 2021; 60: 497–507.

[7] Wang L, Sun Y, Guo Z, Liu H. COL3A1 overexpression associates with poor prognosis and cisplatin resistance in lung cancer. Balkan Medical Journal. 2022; 39: 393–400.

[8] Zhou J, Yang Y, Zhang H, Luan S, Xiao X, Li X, et al. Overexpressed COL3a1 has prognostic value in human esophageal squamous cell carcinoma and promotes the aggressiveness of esophageal squamous cell carcinoma by activating the NF-κB pathway. Biochemical and Biophysical Research Communications. 2022; 613: 193–200.

[9] Li Y, He LR, Gao Y, Zhou NN, Liu Y, Zhou XK, et al. CHD1L contributes to cisplatin resistance by upregulating the ABCB1-NF-κB axis in human non-small-cell lung cancer. Cell Death & Disease. 2019; 10: 99.

[10] Xu B, Wang S, Li R, Chen K, He L, Deng M, et al. Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2. Cell Death & Disease. 2017; 8: e2797.

[11] Jin Y, Sun L, Liu KC. Effect of sufentanil on the viability and apoptosis of cervical cancer cells via the inactivation of PI3K/AKT/mTOR signaling pathway. European Journal of Gynaecological Oncology. 2021; 42: 325–332.

[12] Huang C, Chen C, Zheng F, Ni X, Lin J, Wu W. ATF3 inhibits the growth and stem cells-like features of SW620 colorectal cancer cells in vitro. Journal of Men’s Health. 2021; 17: 287–294.

[13] Yang X, Gong J, Cai X, Yuan Y. Overexpression of HIC1 plays a protective effect on renal cell injury caused by lipopolysaccharide by inhibiting IL-6/STAT3 pathway. Signa Vitae. 2022; 18: 147–453.

[14] Manríquez-Olmos L, Garrocho-Rangel A, Pozos-Guillén A, Ortiz-Magdaleno M, Escobar-García DM. Effect of tricalcium silicate cements in gene expression of COL1A1, MAPK’s, and NF-kB, and cell adhesion in primary teeth’ pulp fibroblasts. Journal of Clinical Pediatric Dentistry. 2022; 46: 17–24.

[15] Liu WH, Lu JJ, Yu RK, Zhou L, Yu Q, Li DF, Zhu QH. LINC00641 regulates prostate cancer cell growth and apoptosis via the miR-365a-3p/VGLL4 axis. European Review for Medical and Pharmacological Sciences. 2021; 25: 108–115.

[16] Liu X, Kong C, Zhang Z. miR-130b promotes bladder cancer cell proliferation, migration and invasion by targeting VGLL4. Oncology Reports. 2018; 39: 2324–2332.

[17] Li N, Yu N, Wang J, Xi H, Lu W, Xu H, et al. miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferation and invasion of gastric cancer cells. American Journal of Cancer Research. 2015; 5: 1158–1168.

[18] Jiao S, Li C, Hao Q, Miao H, Zhang L, Li L, et al. VGLL4 targets a TCF4-TEAD4 complex to coregulate Wnt and Hippo signalling in colorectal cancer. Nature Communications. 2017; 8: 14058.

[19] Zhang W, Gao Y, Li P, Shi Z, Guo T, Li F, et al. VGLL4 functions as a new tumor suppressor in lung cancer by negatively regulating the YAP-TEAD transcriptional complex. Cell Research. 2014; 24: 331–343.

[20] Zhai J, Jiang JF, Shi L. Lycorine weakens tamoxifen resistance of breast cancer via abrogating HAGLR-mediated epigenetic suppression on VGLL4 by DNMT1. Kaohsiung Journal of Medical Sciences. 2023; 39: 278–289.

[21] Hu J, Ruan J, Liu X, Xiao C, Xiong J. MicroRNA-301a-3p suppressed the progression of hepatocellular carcinoma via targeting VGLL4. Pathology, Research and Practice. 2018; 214: 2039–2045.

[22] Januchowski R, Świerczewska M, Sterzyńska K, Wojtowicz K, Nowicki M, Zabel M. Increased expression of several collagen genes is associated with drug resistance in ovarian cancer cell lines. Journal of Cancer. 2016; 7: 1295–1310.

[23] Jiang XM, Xu YL, Yuan LW, Zhang LL, Huang MY, Ye ZH, et al. TGFβ2-mediated epithelial-mesenchymal transition and NF-κB pathway activation contribute to osimertinib resistance. Acta Pharmacologica Sinica. 2021; 42: 451–459.

[24] Xue W, Meylan E, Oliver TG, Feldser DM, Winslow MM, Bronson R, et al. Response and resistance to NF-κB inhibitors in mouse models of lung adenocarcinoma. Cancer Discovery. 2011; 1: 236–247.

[25] Xiao L, Lan X, Shi X, Zhao K, Wang D, Wang X, et al. Cytoplasmic RAP1 mediates cisplatin resistance of non-small cell lung cancer. Cell Death & Disease. 2017; 8: e2803.

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