It is known that miR-381 plays a therapeutic role in a variety of cancers, but the regulatory mechanism of miR-381 in the treatment of lung cancer remains unclear. This study is aimed at exploring the expression level and mechanism of miR-381 in lung cancer. In this experiment, quantitative real-time PCR (qRT-PCR), western blot, and other methods were used to detect the expression of miR-381 and ubiquitin-specific protease 39 (USP39) in lung cancer tissues. The target genes of miR-381 were predicted by bioinformatics techniques, and the targeting relationship between miR-381 and USP39 was verified by the dual-luciferase reporting method. The expression levels of miR-381 and USP39 were adjusted to verify the effect of miR-381 on the expression of USP39 gene. The effect of miR-381 expression on proliferation of lung cancer cells was verified by cell proliferation and invasion experiments. miR-381 was downregulated in non-small-cell lung cancer tissues and cell lines, while USP39 was upregulated. The dual-luciferase reporter gene assay showed that miR-381 and USP39 had targeted binding sites. After transfection with miR-381 mimics, USP39 expression was significantly decreased, cell proliferation decreased, and apoptosis increased. After transfection with miR-381 inhibitor, USP39 expression was significantly increased, cell proliferation increased, and cell apoptosis decreased. Overexpression of USP39 significantly increased the invasion ability and cell survival curve ( p < 0.05 ). In conclusion, overexpression of miR-381 can regulate the expression of USP39, inhibit the proliferation and invasion of cancer cells, and induce apoptosis of cancer cells. This may provide a new perspective and strategy for targeted therapy of non-small-cell lung cancer.

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Background Efforts to precisely assess tumor-specific T-cell immune responses still face major challenges, and the potential molecular mechanisms mediating hepatocellular carcinoma (HCC) microenvironment imbalance after incomplete radiofrequency ablation (iRFA) are unclear. This study aimed to provide further insight into the integrated transcriptomic and proteogenomic landscape and identify a new target involved in HCC progression following iRFA. Methods Peripheral blood and matched tissue samples were collected from 10 RFA-treated HCC patients. Multiplex immunostaining and flow cytometry were used to assess local and systemic immune responses. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. Proteinase-3 (PRTN3) was identified in these analyses. And then, the ability of PRTN3 to predict overall survival (OS) was assessed in 70 HCC patients with early recurrence after RFA. In vitro CCK-8, wound healing and transwell assays were conducted to observe interactions between Kupffer cells (KCs) and HCC cells induced by PRTN3. The protein levels of multiple oncogenic factors and signaling pathway components were detected by western blotting. A xenograft mouse model was built to observe the tumorigenic effect of PRTN3 overexpression on HCC. Results Multiplex immunostaining revealed no immediate significant change in local immune cell counts in periablational tumor tissues after 30 min of iRFA. Flow cytometry showed significantly increased levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127− Tregs and significantly decreased the levels of CD16+CD56+ natural killer cells on day 5 after cRFA (p < 0.05). Transcriptomics and proteomics revealed 389 DEGs and 20 DEPs. Pathway analysis showed that the DEP-DEGs were mainly enriched in the immunoinflammatory response, cancer progression and metabolic processes. Among the DEP-DEGs, PRTN3 was persistently upregulated and closely associated with the OS of patients with early recurrent HCC following RFA. PRTN3 expressed in KCs may affect the migration and invasion of heat stress-treated HCC cells. PRTN3 promotes tumor growth via multiple oncogenic factors and the PI3K/AKT and P38/ERK signaling pathways. Conclusions This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of the HCC milieu induced by iRFA, revealing that PRTN3 promotes HCC progression after iRFA. Trial registration ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588.

Background: Efforts to precisely assess tumor-specific T-cell immune responses capable of mediating imbalanced hepatocellular carcinoma (HCC) ecosystems after incomplete radiofrequency ablation (iRFA) still face major challenges. Here, we assessed the immune response and performed transcriptomic and proteomic analyses in patients with HCC following iRFA. Methods: Peripheral blood and tissue samples were collected from HCC patients who underwent RFA. Multiplex immunostaining and flow cytometry were used to assess the local and systemic immune response. Differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were explored via transcriptomic and proteogenomic analyses. The ability of proteinase-3 (PRTN3) to predict overall survival (OS) was assessed in HCC patients with early recurrence after RFA. Results: Multiplex immunostaining revealed no immediate significant change in local immune cell counts. Flow cytometry analysis showed that the levels of CD4+ T cells, CD4+CD8+ T cells, and CD4+CD25+CD127- Treg cells were significantly increased, while the levels of CD16+CD56+ natural killer cells were significantly decreased on day 5 after cRFA (P<0.05). Transcriptomics and proteomics allow the identification of hundreds of DEGs and DEPs. Pathways related to immunoinflammation response, cancer progression and metabolism were found to be dysregulated at the transcriptomic and proteomic levels. Proteinase 3 (PRTN3) was observed to be persistently upregulated at the gene and protein levels and closely associated with the OS of early recurrent HCC following RFA. Conclusion: This study provides a comprehensive overview of the immune response and transcriptomic and proteogenomic landscapes of HCC milieus, revealing the mechanisms involved in the iRFA-induced immune response and tumor progression. Trial registration: ChiCTR2200055606, http://www.chictr.org.cn/showproj.aspx?proj=32588.