骨架蛋白MYH9和Palladin在肺癌发生发展中的联合作用和临床价值

doi:10.3969/j.issn.1004-616x.2024.05.001

Abstract

Abstract: OBJECTIVE： This study aimed to investigate the combined effects and clinical value of the cytoskeletal proteins MYH9 and Palladin on prognosis and malignant phenotypes in lung cancer. METHODS： Transcriptomic data of lung cancer，along with relevant clinical information，were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatics analyses were conducted to assess the influence of MYH9 and Palladin on lung cancer prognosis and clinical staging，and to further analyze their combined effects on lung cancer prognosis. NCI-H460 cells with double and single knockdowns of MYH9 and Palladin were constructed. The effects of these gene knockdowns on lung cancer cell proliferation，drug resistance，migration，invasion，and self-renewal were evaluated using the CCK-8 assay，transwell assays，and methylcellulose sphere formation assay，respectively. Finally，the expression of MYH9 and Palladin in lung cancer and their influence on patient prognosis were further verified by tissue microarray. RESULTS： The analysis of biological information revealed that MYH9 and Palladin were markedly expressed in lung cancer tissues. Patients in the high expression group of MYH9 and Palladin exhibited a worse prognosis and clinical stage compared to those in the low expression group. Furthermore，the combined high expression group demonstrated the poorest prognosis for lung cancer patients (P<0.01). Results from the cell cuture experiment demonstrated that the proliferation，drug resistance，migration，invasion，and self-renewal ability of lung cancer cells in the bimolecular knockout group were significantly lower than those in the single-molecule knockout group and the control cells (P<0.01). Results from the tissue microarray further confirmed that MYH9 and Palladin were highly expressed in lung cancer tissues in comparison to adjacent paracancerous tissues. In comparison to the low expression group，the prognosis of lung cancer patients in the high expression group of MYH9 and Palladin was worse，and the bimolecular combination of high expression group had a more significant effect on the clinical prognosis of lung cancer patients. CONCLUSION： The combined effect of MYH9 and Palladin on clinical prognosis in lung cancer was more pronounced than their individual effects. Additionally，their combined impact on stemness-related characteristics in lung cancer cells was significantly greater than that of either MYH9 or Palladin alone. These findings suggest that MYH9 and Palladin could potentially serve as combined therapeutic targets for non-small cell lung cancer.

Key words: MYH9, Palladin, lung cancer, stemness-related characteristics, combined effect

CLC Number:

R734.2

LIU Shiya, CHEN Meng, SHEN Gaigai, CAO Yuanting, SUN Lixin, RAN Yuliang. The combined effect and clinical value of cytoskeletal proteins MYH9 and Palladin in lung cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2024, 36(5): 333-341.

References

[1] THAI A A, SOLOMON B J, SEQUIST L V, et al. Lung cancer[J]. Lancet, 2021, 398(10299): 535-554.
[2] SAHU P, DONOVAN C, PAUDEL K R, et al. Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions[J]. Front Oncol, 2023, 13: 1260411.
[3] 郑荣寿, 陈茹, 韩冰峰, 等. 2022年中国恶性肿瘤流行情况分析[J]. 中华肿瘤杂志, 2024, 46(3): 221-231.
[4] GLOBAL BURDEN OF DISEASE CANCER COLLABO-RATION, FITZMAURICE C, ABATE D, et al. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2017: a systematic analysis for the global burden of disease study[J]. JAMA Oncol, 2019, 5(12): 1749-1768.
[5] BLANDIN KNIGHT S, CROSBIE P A, BALATA H, et al. Progress and prospects of early detection in lung cancer[J]. Open Biol, 2017, 7(9): 170070.
[6] FLETCHER D A, MULLINS R D. Cell mechanics and the cytoskeleton[J]. Nature, 2010, 463(7280): 485-492.
[7] YILMAZ M, CHRISTOFORI G. EMT, the cytoskeleton, and cancer cell invasion[J]. Cancer Metastasis Rev, 2009, 28(1/2): 15-33.
[8] LIU X G, NIE L T, ZHANG Y L, et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis[J]. Nat Cell Biol, 2023, 25(3): 404-414.
[9] PETTEE K M, BECKER K N, ALBERTS A S, et al. Targeting the mDia formin-assembled cytoskeleton is an effective anti-invasion strategy in adult high-grade glioma patient-derived neurospheres[J]. Cancers, 2019, 11(3): 392.
[10] SULLIVAN W J, MULLEN P J, SCHMID E W, et al. Extracellular matrix remodeling regulates glucose metabolism through TXNIP destabilization[J]. Cell, 2018, 175(1): 117-132.
[11] SHU X, CHEN M, LIU S Y, et al. Palladin promotes cancer stem cell-like properties in lung cancer by activating Wnt/Β-Catenin signaling[J]. Cancer Med, 2023, 12(4): 4510-4520.
[12] CHEN M, SUN L X, YU L, et al. MYH9 is crucial for stem cell-like properties in non-small cell lung cancer by activating mTOR signaling[J]. Cell Death Discov, 2021, 7(1): 282.
[13] MAK M P, TONG P, DIAO L X, et al. A patient-derived, pan-cancer EMT signature identifies global molecular alterations and immune target enrichment following epithelial-to-mesenchymal transition[J]. Clin Cancer Res, 2016, 22(3): 609-620.
[14] MIRANDA A, HAMILTON P T, ZHANG A W, et al. Cancer stemness, intratumoral heterogeneity, and immune response across cancers[J]. Proc Natl Acad Sci USA, 2019, 116(18): 9020-9029.
[15] HEUZé M L, SANKARA NARAYANA G H N, D’ALESSANDRO J, et al. Myosin II isoforms play distinct roles in adherens junction biogenesis[J]. eLife, 2019, 8: e46599.
[16] YOU G R, CHANG J T, LI Y L, et al. MYH9 facilitates cell invasion and radioresistance in head and neck cancer via modulation of cellular ROS levels by activating the MAPK-Nrf2-GCLC pathway[J]. Cells, 2022, 11(18): 2855.
[17] 刘芳, 彭岚竹, 席菁乐. 高表达MYH9通过激活AKT/c-Myc通路抑制非小细胞肺癌细胞凋亡[J]. 南方医科大学学报, 2023, 43(4): 527-536.
[18] ZHANG Q, FENG P, ZHU X H, et al. DNAJA4 suppresses epithelial-mesenchymal transition and metastasis in nasopharyngeal carcinoma via PSMD2-mediated MYH9 degradation[J]. Cell Death Dis, 2023, 14(10): 697.
[19] ALBRAIKI S, AJIBOYE O, SARGENT R, et al. Functional comparison of full-length palladin to isolated actin binding domain[J]. Protein Sci, 2023, 32(5): e4638.
[20] GILAM A, CONDE J, WEISSGLAS-VOLKOV D, et al. Local microRNA delivery targets Palladin and prevents metastatic breast cancer[J]. Nat Commun, 2016, 7: 12868.
[21] ALEXANDER J I, VENDRAMINI-COSTA D B, FRANCESCONE R, et al. Palladin isoforms 3 and 4 regulate cancer-associated fibroblast pro-tumor functions in pancreatic ductal adenocarcinoma[J]. Sci Rep, 2021, 11(1): 3802.
[22] MAYER O, BUGIS J, KOZLOVA D, et al. Cytoskeletal protein palladin in adult gliomas predicts disease incidence, progression, and prognosis[J]. Cancers, 2022, 14(20): 5130.
[23] MANSOUR M A, ASANO E, HYODO T, et al. Special AT-rich sequence-binding protein 2 suppresses invadopodia formation in HCT116 cells via palladin inhibition[J]. Exp Cell Res, 2015, 332(1): 78-88.
[24] KATONO K, SATO Y, JIANG S X, et al. Prognostic significance of MYH9 expression in resected non-small cell lung cancer[J]. PLoS One, 2015, 10(3): e0121460.
[25] BUTTERFIELD L H, NAJJAR Y G. Immunotherapy combination approaches: mechanisms, biomarkers and clinical observations[J]. Nat Rev Immunol, 2024, 24(6): 399-416.
[26] WAHIDA A, BUSCHHORN L, FR-HLING S, et al. The coming decade in precision oncology: six riddles[J]. Nat Rev Cancer, 2023, 23(1): 43-54.
[27] MEGYESFALVI Z, GAY C M, POPPER H, et al. Clinical insights into small cell lung cancer: tumor heterogeneity, diagnosis, therapy, and future directions[J]. CA Cancer J Clin, 2023, 73(6): 620-652.
[28] ROSSI M, ALTEA-MANZANO P, DEMICCO M, et al. PHGDH heterogeneity potentiates cancer cell dissemination and metastasis[J]. Nature, 2022, 605(7911): 747-753.
[29] VISVADER J E, LINDEMAN G J. Cancer stem cells: current status and evolving complexities[J]. Cell Stem Cell, 2012, 10(6): 717-728.
[30] LI Y T, YAN B S, HE S M. Advances and challenges in the treatment of lung cancer[J]. Biomedecine Pharmacother, 2023, 169: 115891.

The combined effect and clinical value of cytoskeletal proteins MYH9 and Palladin in lung cancer

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