Abstract：Objective: To elucidate the underlying mechanism of the long non-coding RNA (lncRNA) lung cancer associated transcript 1 (LUCAT1) on non-small cell lung cancer (NSCLC). Methods: RT-qPCR and Western blot were used to determine gene and protein expression levels.Dual-luciferase reporter gene (DLRG) was used to verify the relationship between miR-493-5p and LUCAT1 or RAC1.CCK-8,colony formation,flow cytometry and Transwell were applied to evaluate the cell biological behaviors.In addition,the biological function of LUCAT1 in NSCLC was investigated by tumor xenograft experiments. Results: The expression of LUCAT1 and RAC1 mRNA was up-regulated in NSCLC tissues and cell lines,and the expression of miR-493-5p was down-regulated (P<0.05); moreover,in NSCLC,it was observed that LUCAT1 was negatively correlated with miR-493-5p and positively correlated with RAC1 mRNA,and miR-493-5p was negatively correlated with RAC1 mRNA (P<0.05).DLRG confirmed the interaction between miR-493-5p and LUCAT1 or RAC1 (P<0.05).Silencing LUCAT1 could significantly up-regulate the level of miR-493-5p and down-regulate the level of RAC1 (P<0.05).Silencing LUCAT1 significantly attenuated cell proliferative viability,decreased invasion abilities,and promoted cell apoptosis (P<0.05).In addition,inhibition of miR-493-5p or overexpression of RAC1 could partially reverse the effects of LUCAT1 silencing on NSCLC cells (P<0.05).In vivo xenograft tumor experiments confirmed that silencing LUCAT1 significantly inhibited the growth of NSCLC tumors in vivo (P<0.05). Conclusion: LUCAT1 silencing inhibits NSCLC tumorigenesis by regulating the miR-493-5p/RAC1 axis.
[1] Reck M,Remon J,Hellmann MD.First-line immunotherapy for non-small-cell lung cancer[J].Clin Oncol,2022,40(6):586-597. [2] Tan YT,Lin JF,Li T,et al.LncRNA-mediated posttranslational modifications and reprogramming of energy metabolism in cancer[J].Cancer Commun (Lond),2021,41(2):109-120. [3] Shen Q,Xu Z,Xu S.Long non-coding RNA LUCAT1 contributes to cisplatin resistance by regulating the miR-514a-3p/ULK1 axis in human non-small cell lung cancer[J].Int Oncol,2020,57(4):967-979. [4] Stavast CJ,Erkeland SJ.The non-canonical aspects of microRNAs:many roads to gene regulation[J].Cells,2019,8(11):1465-1464. [5] Zhang C,Wu S,Song R,et al.Long noncoding RNA NR2F1-AS1 promotes the malignancy of non-small cell lung cancer via sponging microRNA-493-5p and thereby increasing ITGB1 expression[J].Aging (Albany NY),2020,13(5):7660-7675. [6] Zhong Y,Lin H,Li Q,et al.Downregulation of long non-coding RNA GACAT1 suppresses proliferation and induces apoptosis of NSCLC cells by sponging microRNA-422a[J].Int Mol Med,2021,47(2):659-667. [7] Gai C,Liu C,Wu X,et al.MT1DP loaded by folate-modified liposomes sensitizes erastin-induced ferroptosis via regulating miR-365a-3p/NRF2 axis in non-small cell lung cancer cells[J].Cell Death Dis,2020,11(9):751-761. [8] Xing C,Sun SG,Yue ZQ,et al.Role of incRNA LUCAT1 in cancer[J].Biomed Pharmacother,2021,134(3):111158-111169. [9] Teng YY,Yu HJ,Ni LY,et al.IncRNA LUCAT1 acts as a potential biomarker and demonstrates malignant biological behaviors in gastric cancer[J].Clin Lab,2021,67(8):25-40. [10] Wang X,Ou H,Zhou L,et al.Long non-coding RNA LUCAT1 promotes the progression of clear cell renal cell carcinoma via the microRNA-375/YAP1 axis[J].Exp Ther Med,2021,22(1):754-767. [11] Dai R,Jiang Q,Zhou Y,et al.Lnc-STYK1-2 regulates bladder cancer cell proliferation,migration,and invasion by targeting miR-146b-5p expression and AKT/STAT3/NF-kB signaling[J].Cancer Cell Int,2021,21(1):408-421. [12] Wang RQ,Long XR,Zhou NN,et al.Lnc-GAN1 expression is associated with good survival and suppresses tumor progression by sponging mir-26a-5p to activate PTEN signaling in non-small cell lung cancer[J].Exp Clin Cancer Res,2021,40(1):51-60. [13] Feng N,Guo Z,Wu X,et al.Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis[J].Respir Res,2021,22(1):248-267.
2022, Vol. 28 
冀公网安备13080202000677号