This study aimed to identify Nuclear-activated miRNA (NAmiRNA) and their target genes linked to the prognosis of Lung adenocarcinoma tumor (LUAD), and provide novel diagnostic and therapeutic targets for this devastating disease.
Methods
Putative target (Messenger RNA)mRNA of the prognostic (MicroRNA)miRNA was obtained by interesting the differentially expressed mRNAs with predicted targets from targetscan database. Functional validation experiments were conducted utilizing LUAD cell lines to corroborate the interactions between the identified miRNA and their target mRNAs. Collect cancer and adjacent tissues from patients to detect the expression of target genes. The effects of miRNA-target gene interactions on LUAD cell growth were investigated by (Cell Counting Kit-8)CCK8, colony formation assay and flow cytometry.
Results
Our findings revealed that both miR-31 and its target gene, ZWINT, were considerably overexpressed in LUAD individuals. The results of qPCR and WB indicated that miR-31 effectively upregulated the expression of (Zeste White 10 interactor)ZWINT. The transfection with miR-31mimic enhanced the activity of LUAD cells and promoted colony growth. Knockdown of ZWINT expression resulted in (G2 to mitosis)G2/M phase cell arrest, concurrent with a decrease in Cyclin B1 and (Cyclin-Dependent Kinase 1)CDK1 proteins.
Conclusion
(nuclear activating mirna-31)NAmiRNA-31 and ZWINT are upregulated in LUAD, suggest their potential as biomarkers for the unfavorable prognosis.
DumaNSantana-DavilaRMolinaJR. Non-Small cell lung cancer: epidemiology, screening, diagnosis, and treatment. Mayo Clin Proc2019; 94: 1623–1640.
3.
SongJSunYCaoH, et al.A novel pyroptosis-related lncRNA signature for prognostic prediction in patients with lung adenocarcinoma. Bioengineered2021; 12: 5932–5949.
4.
LiuXXiXXuS, et al.Targeting T cell exhaustion: emerging strategies in non-small cell lung cancer. Front Immunol2024; 15: 1507501.
5.
XuSLuZ. Exploring FNDC4 as a biomarker for prognosis and immunotherapy response in lung adenocarcinoma. Asian J Surg2025; 48: 1799–1801.
6.
XuSLuZ. The role of LMNB2 as a diagnostic and prognostic biomarker in lung adenocarcinoma. Asian J Surg2025; 48: 1175–1177.
7.
ZenginTÖnal-SüzekT. Analysis of genomic and transcriptomic variations as prognostic signature for lung adenocarcinoma. BMC Bioinformatics2020; 21: 368.
8.
ZhuGLuoHFengY, et al.HOXBLINC Long non-coding RNA activation promotes leukemogenesis in NPM1-mutant acute myeloid leukemia. Nat Commun2021; 12: 1956.
9.
LiangYXuPZouQ, et al.An epigenetic perspective on tumorigenesis: loss of cell identity, enhancer switching, and NamiRNA network. Semin Cancer Biol2022; 83: 596–604.
10.
LiuSHeXDiY, et al.NamiRNA-enhancer network of miR-492 activates the NR2C1-TGF-β/Smad3 pathway to promote epithelial-mesenchymal transition of pancreatic cancer. Carcinogenesis2023; 44: 153–165.
11.
LuoJXiaLZhangL, et al.MiRNA-144-5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells. Mutat Res2022; 825: 111798.
12.
SongYKelavaLKissI. MiRNAs in lung adenocarcinoma: role, diagnosis, prognosis, and therapy. Int J Mol Sci2023; 24: 13302.
13.
ZhaoSYuM. Identification of MMP1 as a potential prognostic biomarker and correlating with immune infiltrates in cervical squamous cell carcinoma. DNA Cell Biol2020; 39: 255–272.
14.
XieWWangBWangX, et al.Nine hub genes related to the prognosis of HBV-positive hepatocellular carcinoma identified by protein interaction analysis. Ann Transl Med2020; 8: 78.
15.
KimJHYounYLeeJC, et al.Involvement of the NF-κB signaling pathway in proliferation and invasion inhibited by zwint-1 deficiency in pancreatic cancer cells. J Cancer2020; 11: 5601–5611.
16.
CaoSXiaoSZhangJ,et al.Identification of the cell cycle characteristics of non-small cell lung cancer and its relationship with tumor immune microenvironment, cell death pathways, and metabolic reprogramming. Front Endocrinol (Lausanne2023; 14: 1147366.
17.
YingHXuZChenM, et al.Overexpression of zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins. Onco Targets Ther2018; 11: 689–702.
18.
MiftakhovaRHedblomASemenasJ, et al.Cyclin A1 and P450 aromatase promote metastatic homing and growth of stem-like prostate cancer cells in the bone marrow. Cancer Res2016; 76: 2453–2464.
19.
ShiYXZhuTZouT, et al.Prognostic and predictive values of CDK1 and MAD2L1 in lung adenocarcinoma. Oncotarget2016; 7: 85235–85243.
20.
PalmaFAffinitoANuzzoS, et al.miR-34c-3p targets CDK1 a synthetic lethality partner of KRAS in non-small cell lung cancer. Cancer Gene Ther2021; 28: 413–426.
21.
ZhangBLiFShiY, et al.Single-cell RNA sequencing integrated with bulk RNA sequencing analysis reveals the protective effects of lactate-mediated lactylation of microglia-related proteins on spinal cord injury. CNS Neurosci Ther2024; 30: e70028.
22.
QiuCWangWXuS, et al.Construction and validation of a hypoxia-related gene signature to predict the prognosis of breast cancer. BMC Cancer2024; 24: 02.
23.
DenisenkoTVBudkevichINZhivotovskyB. Cell death-based treatment of lung adenocarcinoma. Cell Death Dis2018; 9: 117.
24.
HuTHanFAnZ. Comprehensive profiling of serum glycosphingolipids to discover the diagnostic biomarkers of lung cancer and uncover the variation of glycosphingolipid networks in different lung cancer subtypes. Anal Methods2024; 16: 7873–7887.
25.
VeljovićE, et al.Artificial neural network and docking study in design and synthesis of xanthenes as antimicrobial agents. In: BadnjevicA (eds) CMBEBIH 2017. IFMBE Proceedings, vol 62. Singapore: Springer, 2017.
26.
BadnjevicACifrekMKorugaD. Classification of chronic obstructive pulmonary disease (COPD) Using integrated software suite. In: Roa RomeroL (eds) XIII Mediterranean conference on medical and biological engineering and computing 2013. IFMBE Proceedings, vol 41. Cham: Springer, 2014.
27.
HafizovićLČauševićADeumićA, et al.The use of artificial intelligence in diagnostic medical imaging: systematic literature review. In: 2021 IEEE 21st international conference on bioinformatics and bioengineering (BIBE), Kragujevac, Serbia, 2021, pp.1–6.
28.
HrvatFSpahićLPokvićLG,et al.Artificial neural networks for prediction of medical device performance based on conformity assessment data: infusion and perfusor pumps case study. In: 2020 9th Mediterranean conference on embedded computing (MECO), Budva, Montenegro, 2020, pp.1–4.
29.
WuXSuiZZhangH, et al.Integrated analysis of lncRNA-mediated ceRNA network in lung adenocarcinoma. Front Oncol2020; 10: 554759.
30.
LinKXuTHeBS, et al.MicroRNA expression profiles predict progression and clinical outcome in lung adenocarcinoma. Onco Targets Ther2016; 9: 5679–5692.
31.
ZhuRWangHLinL. Prognostic and clinicopathological value of ZWINT expression levels in patients with lung adenocarcinoma: a systematic review and meta-analysis. Clinics (Sao Paulo)2021; 76: e3222.
32.
XingZLuoZYangH, et al.Screening and identification of key biomarkers in adrenocortical carcinoma based on bioinformatics analysis. Oncol Lett2019; 18: 4667–4676.
33.
GreenawaltEJEdmondsMDJainN, et al.Targeting of SGK1 by miR-576-3p inhibits lung adenocarcinoma migration and invasion. Mol Cancer Res2019; 17: 289–298.
34.
WangBBXieHWuT, et al.Controlled-release mitomycin C-polylactic acid film prevents epidural scar hyperplasia after laminectomy by inducing fibroblast autophagy and regulating the expression of miRNAs. Eur Rev Med Pharmacol Sci2017; 21: 2526–2537.
35.
LiHNZhengWHDuYY, et al.ZW10 Interacting kinetochore protein may serve as a prognostic biomarker for human breast cancer: an integrated bioinformatics analysis. Oncol Lett2020; 19: 2163–2174.
36.
TerranoDTUpretiMChambersTC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol2010; 30: 640–656.
