Comprehensively analysis of IL33 in hepatocellular carcinoma prognosis, immune microenvironment and biological role.

IL33 plays an important role in cancer. However, the role of liver cancer remains unclear. Open-accessed data was obtained from the Cancer Genome Atlas, Xena, and TISCH databases. Different algorithms and R packages are used to perform various analyses. Here, in our comprehensive study on IL33 in HCC, we observed its differential expression across cancers, implicating its role in cancer development. The single-cell analysis highlighted its primary expression in endothelial cells, unveiling correlations within the HCC microenvironment. Also, the expression level of IL33 was correlated with patients survival, emphasizing its potential prognostic value. Biological enrichment analyses revealed associations with stem cell division, angiogenesis, and inflammatory response. IL33's impact on the immune microenvironment showcased correlations with diverse immune cells. Genomic features and drug sensitivity analyses provided insights into IL33's broader implications. In a pan-cancer context, IL33 emerged as a potential tumour-inhibitor, influencing immune-related molecules. This study significantly advances our understanding of IL33 in cancer biology. IL33 exhibited differential expression across cancers, particularly in endothelial cells within the HCC microenvironment. IL33 is correlated with the survival of HCC patients, indicating potential prognostic value and highlighting its broader implications in cancer biology.

Unveiling the role of the KLF4/Lnc18q22.2/ULBP3 axis in the tumorigenesis and immune escape of hepatocellular carcinoma under hypoxic condition.

Hepatocellular carcinoma (HCC) represents a significant global health burden, necessitating an in-depth exploration of its molecular underpinnings to facilitate the development of effective therapeutic strategies. This investigation delves into the complex role of long non-coding RNAs (lncRNAs) in the modulation of hypoxia-induced HCC progression, with a specific emphasis on delineating and functionally characterizing the novel KLF4/Lnc18q22.2/ULBP3 axis. To elucidate the effects of hypoxic conditions on HCC cells, we established in vitro models under both normoxic and hypoxic environments, followed by lncRNA microarray analyses. Among the lncRNAs identified, Lnc18q22.2 was found to be significantly upregulated in HCC cells subjected to hypoxia. Subsequent investigations affirmed the oncogenic role of Lnc18q22.2, highlighting its critical function in augmenting HCC cell proliferation and migration. Further examination disclosed that Kruppel-like factor 4 (KLF4) transcriptionally governs Lnc18q22.2 expression in HCC cells, particularly under hypoxic stress. KLF4 subsequently enhances the tumorigenic capabilities of HCC cells through the modulation of Lnc18q22.2 expression. Advancing downstream in the molecular cascade, our study elucidates a novel interaction between Lnc18q22.2 and UL16-binding protein 3 (ULBP3), culminating in the stabilization of ULBP3 protein expression. Notably, ULBP3 was identified as a pivotal element, exerting dual functions by facilitating HCC tumorigenesis and mitigating immune evasion in hypoxia-exposed HCC cells. The comprehensive insights gained from our research delineate a hitherto unidentified KLF4/Lnc18q22.2/ULBP3 axis integral to the understanding of HCC tumorigenesis and immune escape under hypoxic conditions. This newly unveiled molecular pathway not only enriches our understanding of hypoxia-induced HCC progression but also presents novel avenues for therapeutic intervention.

Small peptide LINC00511-133aa encoded by LINC00511 regulates breast cancer cell invasion and stemness through the Wnt/ß-catenin pathway.

LINC00511 is an long non-coding RNA (lncRNA) of ncRNAs,This study aimed to investigate whether the lncRNA LINC00511 could encode a small peptide, LINC00511-133aa, and whether this peptide could promote breast cancer cell metastasis and stemness by activating the wnt/ß-catenin pathway. The LINC00511-133aa coding sequence vector and control vector were transfected into MCF-7 and MDA-MB-231 breast cancer cells, with subsequent assessment of peptide expression using PCR, western blotting, and immunofluorescence assays. Cell proliferation, invasion, and apoptosis were evaluated using CCK8, apoptotic, wound healing, and transwell invasion assays, while the characteristic changes of tumor stem cells were detected through sphere-forming assay and western blot analyses of the stemness markers Oct4, Nanog, and SOX2. Results showed that LINC00511-133aa was indeed encoded by LINC00511 and promoted the invasiveness and stemness of breast cancer cells while limiting apoptosis by modulating the expression levels of wnt/ß-catenin pathway-related proteins Bax, c-myc, and CyclinD1, as well as facilitating ß-catenin protein entry into the nucleus. This study provides evidence for the potential involvement of lncRNA LINC00511 and its peptide product in breast cancer progression via the regulation of the wnt/ß-catenin pathway.

AKR1C1 Contributes to Cervical Cancer Progression via Regulating TWIST1 Expression.

Cervical cancer (CC) is a common gynecological malignancy, accounting for 10% of all gynecological cancers. Recently, targeted therapy for CC has shown unprecedented advantages. To improve CC patients' prognosis, there are still urgent needs to develop more promising therapeutic targets. Aldo-keto reductase 1 family member C1 (AKR1C1) is a type of aldosterone reductase and plays a regulatory role in a variety of key metabolic pathways. Several studies indicated that AKR1C1 was highly expressed in a series of tumors, and participated in the progression of these tumors. However, the possible effects of AKR1C1 on CC progression remain unclear. Herein, we revealed AKR1C1 was highly expressed in human CC tissues and correlated with the clinical characteristics of patients with CC. AKR1C1 could regulate the proliferation and invasion of cervical cancer cells in vitro. Further experiments showed that AKR1C1 could regulate TWIST1 expression and AKT pathway. In summary, we confirmed the involvement of AKR1C1 in CC progression, and therefore AKR1C1 may have the potential to be a molecular target for CC treatment.

Co-expressing LRP6 With Anti-CD19 CAR-T Cells for Improved Therapeutic Effect Against B-ALL.

BACKGROUND: Cellular immunotherapies, such as chimeric antigen receptor modified-T cell (CAR-T) therapy, offers excellent potential for tumor treatment. The memory phenotype of CAR-T has been correlated positively with a therapeutic effect on and prognosis of cancer. METHOD: The proliferation rates of novel CAR-T was determined by cell counting. The phenotypes of CAR-T cells were then detected by flow cytometry. The cell cytotoxicity against tumor cells in vitro was investigated by lactate dehydrogenase assay and luciferase assay. The cytokines secreted during these assays were determined by the cytometric bead array assay. The antitumor ability in vivo was evaluated in NOG mice. RESULTS: Co-expression of an LRP6 full-length protein with anti-CD19 CAR significantly improved the memory phenotype of CAR-positive T-cells by enhancing the wnt signaling pathway. As compared with anti-CD19 CAR-T, anti-CD19 CAR-T-LRP6 exhibited more robust cytotoxicity against tumor cells in vitro and in vivo, albeit fewer cytokines were released in vitro. Moreover, the longer survival rate and robust expansion in vivo of anti-CD19 CAR-T-LRP6 cells were found to be effective in inhibiting cancer recurrence. CONCLUSIONS: CAR co-expressed with LRP6 could sustain the memory phenotype that enabled permanent relief and may further assist in the development of potent and durable T-cell therapeutics.

Genetic variants in IL-33/ST2 pathway with the susceptibility to hepatocellular carcinoma in a Chinese population.

Interleukin (IL)-33/ST2 pathway plays a pivotal role in tumorigenesis through influencing cancer stemness, tumor growth, metastasis, angiogenesis, and accumulation of regulatory T cells in tumor microenvironments. The aim of this study was to investigate the association of IL-33 rs7025417 and ST2 rs3821204 with the risk of hepatocellular carcinoma (HCC). Genotyping of IL-33 rs7025417 and ST2 rs3821204 was carried out using a Taqman assay. IL-33 and ST2 mRNA was examined using real-time PCR and plasma IL-33 and sST2 levels were measured using enzyme-linked immunosorbent assay. The ST2 rs3821204 CC genotype was associated with a significantly increased risk of HCC (CC vs. GG: adjusted OR = 2.29, 95% CI, 1.39-3.78; dominant model: adjusted OR = 1.58, 95% CI, 1.12-2.23; recessive model: adjusted OR = 1.88, 95% CI, 1.21-2.93; C vs. G: adjusted OR = 1.53, 95% CI, 1.20-1.95). Gene-environment interaction analysis showed that the risk effect of rs3821204 CG/CC genotypes was more evident in smokers (adjusted OR = 1.70, 95% CI, 1.13-2.55) and drinkers (adjusted OR = 1.57, 95% CI, 1.04-2.37). The increased risk was also observed in combined analysis. Moreover, HCC patients with ST2 rs3821204 CC genotype had higher levels of mRNA and protein expression (P < 0.05). These findings suggest that ST2 rs3821204 CC genotype may contribute to hepatocarcinogenesis by enhancing ST2 production at the transcriptional and translational level.