Studies have shown that SQLE is highly expressed in a variety of tumours and promotes tumour progression. However, the role of SQLE in pancreatic cancer (PC) has not been reported. Here, we aim to study the role and molecular mechanism of SQLE in PC. Immunohistochemistry and functional experiments showed that SQLE was highly expressed in PC tissues and promoted the proliferation and invasion of PC cells. Terbinafine, an inhibitor of SQLE, inhibited this effect. In order to further study the upstream mechanism that regulates SQLE, we used bioinformatics technology to lock miR‐133b and lncRNA‐TTN‐AS. In situ hybridization was used to detect the expression of miR‐133b and lncRNA‐TTN‐AS1 in PC tissues. The luciferase reporter gene experiment was used to confirm the binding of miR‐133b and lncRNA‐TTN‐AS1. The results showed that miR‐133b was down‐regulated in PC tissues and negatively correlated with the expression of SQLE. LncRNA‐TTN‐AS1 was upregulated in pancreatic cancer tissues and positively correlated with the expression of SQLE. Luciferase gene reporter gene analysis confirmed lncRNA‐TTN‐AS1 directly binded to miR‐133b. Therefore, we propose that targeting the lncRNA‐TTN‐AS1/miR‐133b/SQLE axis is expected to provide new ideas for the clinical treatment of PC patients.

Background: Using Mendelian randomization research, several specialists are now curious to learn more about the association between gut bacteria and lung cancer and its subtypes. However, their GWAS summary statistics and statistical methodologies are outdated and constrained. Methods: A two-sample bidirectional Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest genome-wide meta-analysis conducted by the MiBioGen. The summary statistics of lung cancer were extracted from the largest lung cancer GWAS meta-analysis.Inverse variance weighted (multiplicative random effects), MR-Egger regression, weighted median, weighted model and MR-PRESSO were used to examine the causal relationship. Reverse MR analysis was also performed on the lung cancer and its subtypes and microbiota. Result:Inverse variance weighted(IVW) estimates suggested that we identified 2 bacterial taxon that were causally associated with lung cancer, 1 bacterial taxon with Lung Adenocarcinoma (LUAD), 3 bacterial taxon with Small Cell Lung Carcinoma (SCLC),1 bacterial taxon with Lung cancer in never smokers (LCNS) and 3 bacterial taxon with Lung cancer in ever smokers (LCES).Also in the reverse MR analysis,we identified 1 bacterial taxon that were causally associated with lung cancer, 5 bacterial taxon with Squamous Cell Lung Carcinoma (LUSC), 1 bacterial taxon with LCNS and 5 bacterial taxon with LCES. Conclusion: In summary, this two-sample MR study found that several gut microbiota taxon was causally associated with lung cancer and its subtypes. Further studies are needed to clarify the effect of gut microbiota on them, including their specific mechanism.