UCHL1 acts as a potential oncogene and affects sensitivity of common anti-tumor drugs in lung adenocarcinoma

Abstract

Background Lung adenocarcinoma is the leading cause of cancer death worldwide. Recently, ubiquitin C-terminal hydrolase L1 (UCHL1) has been demonstrated to be highly expressed in many tumors and plays the role of an oncogene. However, the functional mechanism of UCHL1 is unclear in lung adenocarcinoma progression. Methods We analyzed the differential expression of the UCHL1 gene in lung adenocarcinoma and normal lung tissues, and the correlation between the UCHL1 gene and prognosis was also analyzed by the bioinformatics database TCGA. Meanwhile, we detected and analyzed the expression of UCHL1 and Ki-67 protein in a tissue microarray (TMA) containing 150 patients with lung adenocarcinoma by immunohistochemistry (IHC) and clinicopathological characteristics by TCGA database. In vitro experiments, we knocked down the UCHL1 gene of A549 cells and detected the changes in cell migration, invasion, and apoptosis. At the same time, we analyzed the effect of UCHL1 on anti-tumor drug sensitivity of lung adenocarcinoma by a bioinformatics database. In terms of the detection rate of lung adenocarcinoma indicators, we analyzed the impact of UCHL1 combined with common clinical indicators on the detection rate of lung adenocarcinoma through a bioinformatics database. Results In this study, the analysis of UCHL1 protein expression in lung adenocarcinoma proved that obviously higher UCHL1 protein level was discovered in lung adenocarcinoma tissues. The expression of UCHL1 was closely related to poor clinical outcomes. Interestingly, a significantly positive correlation between the expression of UCHL1 and Ki-67-indicated UCHL1 was associated with tumor migration and invasion. Through executing loss of function tests, we affirmed that silencing of UCHL1 expression significantly inhibited migration and invasion of lung adenocarcinoma cells in vitro. Furthermore, lung adenocarcinoma cells with silenced UCHL1 showed a higher probability of apoptosis. In terms of the detection rate of lung adenocarcinoma indicators, we discovered UCHL1 could improve the detection rate of clinical lung adenocarcinoma and affect drug sensitivity. Conclusion In lung adenocarcinoma, UCHL1 promotes tumor migration, invasion, and metastasis by inhibiting apoptosis and has an important impact on the clinical drug treatment of lung adenocarcinoma. In addition, UCHL1 can improve the detection rate of clinical lung adenocarcinoma. Above all, UCHL1 may be a new marker for the diagnosis of lung adenocarcinoma and provide a new target for the treatment of clinical diseases.

Multi-Omics Analysis Revealed a Significant Alteration of Critical Metabolic Pathways Due to Sorafenib-Resistance in Hep3B Cell Lines

“…UCHL1 plays a vital role in anti-apoptosis, cancer cell invasion, migration and proliferation. Moreover, it enhances the multi-drug resistance in different cancer cells and tissues [ 73 , 74 , 75 ]. A previous study showed that UCHL1 overexpression supported apoptosis in verapamil- and Adriamycin-treated hepatoma cell lines (BEL-7402 and SMMC-7721) [ 76 ].…”

“…Knockdown of UCHL1 by siRNA attenuated the cell apoptosis effect of combined drugs, which indicated the important role of UCHL1 in the verapamil-mediated reversal of drug resistance [ 76 ]. In another study, UCHL1 overexpression improves the early diagnosis and detection rate and provides targeted drug therapy for lung adenocarcinoma [ 75 ]. The underlying mechanism of UCHL1 mediated MDR to P-glycoprotein (P-gp) substrate drugs and the increased invasion and migration in resistant breast cancer cells compared to the sensitive phenotype, which might be associated with MAPK/Erk pathway activation [ 74 ].…”

Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

“…162 In lung adenocarcinoma, UCHL1 promotes tumor metastasis, inhibits apoptosis, and is significantly involved in patient prognosis. 163 In line with these findings, the knockdown of UCHL1 was recently reported to limit the proliferation and migration of HN6 HNSCC cells. 158 Nevertheless, there are contradicting data demonstrating that exogenous expression of UCHL1 inhibited the proliferation of LNCaP prostate cancer cells via p53-induced Akt inhibition as well as p27 accumulation.…”

“…Further, silencing UCHL1‐mediated reduction of uterine serous carcinoma cell proliferation is carried out through attenuating cyclin‐B1 expression as well as cell cycle progression 162 . In lung adenocarcinoma, UCHL1 promotes tumor metastasis, inhibits apoptosis, and is significantly involved in patient prognosis 163 . In line with these findings, the knockdown of UCHL1 was recently reported to limit the proliferation and migration of HN6 HNSCC cells 158 .…”

Vimentin‐positive invasive breast carcinoma of no special type: A breast carcinoma with lethal biological characteristics

“…GABRP, BCL11A, and UCHL1 have been reported as key-coding RNAs that play important roles in inducing resistance of carcinoma cells to chemoendocrine therapy and/or radiotherapy. [27][28][29] In addition, since GABRP, MMP7, and CYP4F3 are known to participate significantly in the tumor immunity of carcinomas of various organs, [30][31][32] these coding RNAs probably are also involved in intensifying the malignant potential of vimentin-positive IBC-NSTs. In this study, although we also examined the tumor specimens for the 58 coding RNAs that have previously been reported as being significantly associated with EMT, only two were found to be significantly upregulated in vimentin-positive IBC-NSTs according to the FDR value (11 according to the p value).…”