miR-15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2.

Lung adenocarcinoma (LUAD) is a subtype of lung cancer (LC), which is the most common tumor worldwide. Accumulating evidence has elucidated an important role of microRNAs (miRNAs) in mediating the development and progression of several tumors. The purpose of this study was to explore the role and underlying mechanism of miR-15b in LUAD. CCK-8 and Transwell assays were conducted to measure the capacities of cell viability and migration in SPC-A1 cells. Luciferase assay was utilized to verifymiR-15b direct binding to BCL2 mRNA 3'-UTR. We determined that miR-15b was overexpressed in LUAD and miR-15b overexpression predicted a significantly worse outcome in patients with LUAD. miR-15b improved LUAD growth in vitro and vivo. miR-15b enhanced cell migration and epithelial-mesenchymal transition (EMT) in LUAD. miR-15b promoted cell viability, migration and EMT through inhibiting BCL2 expression by targeting to its mRNA 3'-UTR. BCL2 reversed functions of miR-15b on promoting cell proliferation, migration and EMT in SPC-A1 cells. miR-15b promoted cell viability, migration and EMT by targeting BCL2 in LUAD. The newly identified miR-15b/BCL2 axis provides a novel insight into the pathogenesis of LUAD.

Wang J ，Yao S ，Diao Y ，Geng Y ，Bi Y ，Liu G ... -  《-》

USF1-induced overexpression of long noncoding RNA WDFY3-AS2 promotes lung adenocarcinoma progression via targeting miR-491-5p/ZNF703 axis.

Ren P ，Hong X ，Chang L ，Xing L ，Zhang H ... -  《-》

MiR-340-3p-HUS1 axis suppresses proliferation and migration in lung adenocarcinoma cells.

The functions and molecular mechanisms of miR-340-3p in lung adenocarcinoma (LUAD) progression remain unclear. On the other hand, the role of HUS1 in LUAD progression should be further explored. Data from cancer database were subjected to bioinformatics analysis. Quantitative real-time PCR and western blot were performed to detect gene expression. Colony formation and MTT assay were performed to examine cell growth in vitro. Wound healing assays and transwell assays were performed to examine cell migration. Here, our results showed that miR-340-3p was lower expressed in LUAD tissues and LUAD-derived cell lines. And miR-340-3p suppressed the proliferation and migration ability of LUAD cells. Further, miR-340-3p inhibits HUS1 expression, which was higher expressed in LUAD tissues and promoted the proliferation and migration ability of LUAD cells. Moreover, higher HUS1 expression was associated with poor survival rate and shorter survival time in patients with LUAD, and HUS1 expression was negative correlated with that of miR-340-3p in clinical samples. In addition, overexpression of HUS1 counteracted the downregulation of cell growth by miR-340-3p. The study mainly indicated that miR-340-3p may play a tumor suppressor role in the progression of LUAD, with the function of restraining HUS1 expression, highlighting a potential therapeutic target for LUAD.

Ren K ，Yu Y ，Wang X ，Liu H ，Zhao J ... -  《-》

Actin-like protein 8 promotes cell proliferation, colony-formation, proangiogenesis, migration and invasion in lung adenocarcinoma cells.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated mortality worldwide of which lung adenocarcinoma (LUAD) is the most common. The identification of oncogenes and effective drug targets is the key to individualized LUAD treatment. Actin-like protein 8 (ACTL8), a member of the cancer/testis antigen family, is associated with tumor growth and patient prognosis in various types of cancer. However, whether ACTL8 is involved in the development of LUAD remains unknown. The aim of the present study was to demonstrate the role of ACTL8 in human LUAD cells. The expression of ACTL8 in LUAD tissues and cell lines was assessed using immunohistochemistry and western blotting. Additionally, plasmids expressing ACTL8-specific short hairpin RNAs were used to generate lentiviruses which were subsequently used to infect A549 and NCI-H1975 human LUAD cells. Cell proliferation, migration, invasion and apoptosis, as well as cell cycle progression and the expression of protein markers of epithelial to mesenchymal transition were investigated. A549 cell tumor growth in nude mice was also examined. The results showed that ACTL8 was highly expressed in A549 and NCI-H1975 LUAD cell lines. Additionally, ACTL8-knockdown inhibited proliferation, colony formation, cell cycle progression, migration and invasion, and increased apoptosis in both cell lines. Furthermore, in vivo experiments in nude mice revealed that ACTL8-knockdown inhibited A549 cell tumor growth. These results suggest that ACTL8 serves an oncogenic role in human LUAD cells, and that ACTL8 may represent a potential therapeutic target for LUAD. Our results suggest that ACTL8 serves an oncogenic role in human LUAD cells, and that ACTL8 may represent a potential therapeutic target for LUAD.

Ma S ，Wang X ，Zhang Z ，Liu D ... -  《-》

Effects of MicroRNA-195-5p on Biological Behaviors and Radiosensitivity of Lung Adenocarcinoma Cells via Targeting HOXA10.

To explore the effects of miR-195-5p and its target gene HOXA10 on the biological behaviors and radiosensitivity of lung adenocarcinoma (LUAD) cells. The effects of miR-195-5p on LUAD cell proliferation, migration, invasion, cycle arrest, apoptosis, and radiosensitivity were investigated by in vitro experiments. The bioinformatics analysis was used to assess its clinical value and predict target genes. Double-luciferase experiments were used to verify whether the miR-195-5p directly targeted HOXA10. A xenograft tumor-bearing mouse model was used to examine its effects on the radiosensitivity of LUAD in vivo. Both gain- and loss-of-function assays demonstrated that miR-195-5p inhibited LUAD cell proliferation, invasion, and migration, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. Double-luciferase experiments confirmed that miR-195-5p directly targeted HOXA10. Downregulation of HOXA10 also inhibited LUAD cell proliferation, migration, and invasion, induced G1 phase arrest and apoptosis, and enhanced radiosensitivity. The protein levels of β-catenin, c-myc, and Wnt1 were decreased by miR-195-5p and increased by its inhibitor. Moreover, the effects of the miR-195-5p inhibitor could be eliminated by HOXA10-siRNA. Furthermore, miR-195-5p improved radiosensitivity of LUAD cells in vivo. miR-195-5p has excellent antitumor effects via inhibiting cancer cell growth, invasion, and migration, arresting the cell cycle, promoting apoptosis, and sensitizing LUAD cells to X-ray irradiation by targeting HOXA10. Thus, miR-195-5p may serve as a potential candidate for the treatment of LUAD.

Yuan C ，Bai R ，Gao Y ，Jiang X ，Li S ，Sun W ，Li Y ，Huang Z ，Gong Y ，Xie C ... -  《-》