LncRNA LASTR promote lung cancer progression through the miR-137/TGFA/PI3K/AKT axis through integration analysis.

Background: Long noncoding RNAs (LncRNAs) are widely involved in the physiological and pathophysiological processes of cells. This study sought to identify novel lncRNAs that play key roles in progression of lung cancer. Methods: Cells were purchased from the Cell Bank of Type Culture Collection of the Chinese Academy of Sciences. Public lung cancer data were retrieved from The Cancer Genome Atlas database. Statistical analyses were performed using SPSS, R and GraphPad Prism 8 software. Results: Bioinformatic analysis showed that the lncRNA, LASTR (ENSG00000242147) was significantly upregulated in lung cancer tissues (LUAD and LUSC) compared with the expression level in adjacent normal tissue. Kaplan-Meier survival analysis showed that patients with higher LASTR expression level had a shorter overall survival and worse clinical features relative to patients with low LASTR expression levels. qRT-PCR results showed that LASTR was highly expressed in lung cancer cell lines relative to the expression level in normal lung epithelial cell line. Cell phenotype experiments indicated that knockdown of LASTR significantly inhibited proliferation and metastatic ability of lung cancer cells. Analysis of the downstream mechanism of LASTR demonstrated that LASTR exerts the oncogene effect through the miR-137/TGFA axis. GSEA results indicated that LASTR exhibits its activity by activating the PI3K/AKT signaling pathway, which was validated by western blotting assay. Conclusion: In summary, the results of the present study showed that LASTR promotes lung cancer progression through miR-137/TGFA/PI3K/AKT axis.

ADCK1 activates the ß-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells.

As a result of mutations in the upstream components of the Wnt/ß-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the ß-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

MLL3 promotes the senescence of esophageal squamous cell carcinoma.

BACKGROUND: Senescence has been recognized as a mechanism for the suppression of tumorigenesis. However, how the senescence is regulated is not fully understood. AIMS: The present study aims to elucidate MLL3-mediated regulation of senescence. MATERIALS AND METHODS: MLL3 protein levels in esophageal squamous cell carcinoma (ESCC) tissues were examined by Western blotting and immunohistochemistry. The effects of MLL3 on the growth and senescence of ESCC cells were examined using MTT assay, soft agar assay, and ß-gal staining. The interaction between MLL3 and P16 was evaluated by immunoprecipitation and GST pull-down assay. RESULTS: In this study, we found that MLL3 promoted the senescence of ESCC cells. MLL3 was downregulated in ESCC. MLL3 inhibited the growth and colony formation of ESCC cells. Mechanistically, MLL3 interacted with P16 and impaired the interaction between P16 and UHRF1 (the E3 ligase for P16), thus upregulating the protein levels of several senescence regulators. CONCLUSION: Collectively, this study demonstrated the regulation of senescence by MLL3.