Clinical roles of the aberrantly expressed lncRNAs in lung squamous cell carcinoma: a study based on RNA-sequencing and microarray data mining Clinical roles of the aberrantly expressed lncRNAs in lung squamous cell carcinoma: a study based on RNA-sequencing and microarray data mining

Identification of lung adenocarcinoma specific dysregulated genes with diagnostic and prognostic value across 27 TCGA cancer types Identification of lung adenocarcinoma specific dysregulated genes with diagnostic and prognostic value across 27 TCGA cancer types

Background: Circular RNA (circRNA) is a novel molecular marker and target candidate that is closely associated with tumor invasion and migration. The mechanism of action of hsa_circ_0005035 (circ‐IGF1R) in non‐small cell lung cancer remains unclear. In this study, we aimed to study the mechanism of action of circ‐IGF1R in lung cancer.Methods: We screened circ‐IGF1R, one of the most notable differential expressions, from the Gene Expression Omnibus database, GSE104854, for further research. The expression level of circ‐IGF1R was examined using quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) in five different lung cancer cell lines and 50 pairs of lung cancer and adjacent tissues. Wound‐healing and Transwell assays were used for verifying the biological function of circ‐IGF1R. The effect of overexpressing circ‐IGF1R on the transcriptome of whole lung cancer cells was explored in lung cancer cell lines using RNA‐seq.Results: The expression level of circ‐IGF1R was notably lower in lung cancer tissues and lung cancer cell lines than in the adjacent normal tissues and cells (P < 0.0001). In addition, the expression level of circ‐IGF1R was associated with larger tumors (T2/T3/T4) and lymph node metastasis (N1/ N2/N3) (P < 0.05). The overexpression of circ‐IGF1R significantly inhibited the invasion and migration of the lung cancer cells. The potential network of circ‐IGF1R–miR‐1270–VANGL2 was preliminarily determined, and the expression patterns of miR‐1270 and VANGL2 were verified in lung cancer cell lines.Conclusion: Circ‐IGF1R may inhibit lung cancer invasion and migration through a potential network of circ‐IGF1R–miR‐1270–VANGL2.

MicroRNA (miRNA) played an important role in the progression of liver cancer and its diagnostic and prognostic values have been frequently studied. However, different microarray techniques and small sample size led to inconsistent findings in previous studies. We performed a comprehensive meta-analysis of a total of 357 tumor and 283 noncancerous samples from 12 published miRNA expression studies using robust rank aggregation method. As a result, we identified a statistically significant meta-signature of five upregulated (miR-221, miR-222, miR-93, miR-21 and miR-224) and four downregulated (miR-130a, miR-195, miR-199a and miR-375) miRNAs. We then conducted miRNA target prediction and pathway enrichment analysis to find what biological process these miRNAs might affect. We found that most of the pathways were frequently associated with cell signaling and cancer pathogenesis. Thus these miRNAs may involve in the onset and progression of liver cancer and serve as potential diagnostic and therapeutic targets of this malignancy.

PIK3CA is a key component of phosphatidylinositol 3-kinase (PI3K) pathway that its involvement in tumorigenesis has been revealed by previous research. However, its functions and potential mechanisms in bladder cancer are still largely undiscovered. Tissue microarray (TMA) with 66 bladder cancer patients was surveyed via immunohistochemistry to evaluate the level of PIK3CA and CUX1 and we found upregulation of PIK3CA in bladder cancer tissue and patients with higher level of PIK3CA presented with poorer prognosis. Overly expressed PIK3CA promoted growth, migration, invasion, and metastasis of bladder cancer cells and knockdown of PIK3CA had the opposite effect. Gain-of-function and loss-of-function studies showed that PIK3CA expression was facilitated by CUX1, leading to activation of epithelial-mesenchymal transition (EMT), accompanied by upregulated expression of Snail, β-catenin, Vimentin and downregulated expression of E-cadherin in the bladder cancer cell lines. Besides, over-expressed CUX1 could restore the expression of downregulated Snail, β-catenin, Vimentin and E-cadherin which was induced by PIK3CA knockdown. These results revealed that PIK3CA overexpression in bladder cancer was regulated by the transcription factor CUX1, and PIK3CA exerted its biological effects by activating EMT.