scholarly journals CDCA attenuates LUAD pathogenesis progression via integrin α5β1/FAK/p53 signalling pathway

2021 ◽  
Author(s):  
Dan Shen ◽  
Yuanyuan Zeng ◽  
Weijie Zhang ◽  
Yue Li ◽  
Jianjie Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Signalling Pathway ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Integrin Α5β1

Abstract BackgroundLung cancer is the leading cause of cancer-associated death and includes non-small-cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC comprises approximately 80–85% of all lung cancers. Chenodeoxycolic acid (CDCA), one of the primary bile acids, has been reported to inhibit proliferation in carcinoma cells. To date, the role of CDCA in the migration, invasion and apoptosis of LUAD remains unknown. MethodsWestern blotting and quantitative real-time PCR were used to test the protein and mRNA expression levels in LUAD cell lines. Cell Counting Kit-8 (CCK-8) and clone formation assays were performed to evaluate the proliferation ability of different kinds of cells in vitro. Transwell assay were utilized to assess the motility of tumor cells. RNA-seq was performed to identify the transcriptional profile in A549 cells after treatment with CDCA. A xenograft model was established to study the effect of CDCA on LUAD growth in vivo. GraphPad Prism 8 software was used for statistical analysis, and a P value < 0.05 was considered statistically significant.ResultsCDCA can significantly inhibited the migration and invasion capabilities of LUAD cells. Furthermore, CDCA promoted the progression of apoptosis in LUAD cells. Mechanistically, we revealed that CDCA blocked the integrin α5β1 signalling pathway by inhibiting the expression of integrin α5 and β1 subunits and p-FAK in LUAD cells. Furthermore, we found that CDCA increased the levels of p53, a downstream gene of the integrin α5β1/FAK pathway. ConclusionOur findings indicated that CDCA attenuates LUAD pathogenesis via the integrin α5β1/FAK/p53 axis in LUAD cells.

scholarly journals Kinesin superfamily protein 21B acts as an oncogene in non-small cell lung cancer

2020 ◽  
Author(s):  
Zhi-Gang Sun ◽  
Feng Pan ◽  
Jing-Bo Shao ◽  
Qian-Qian Yan ◽  
Lu Lu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Nude Mice ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Kinesin Superfamily

Abstract Background: Kinesin superfamily proteins (KIFs) serve as microtubule-dependent molecular motors, and are involved in the progression of many malignant tumors. In this study, we aimed to investigate the expression pattern and precise role of kinesin family member 21B (KIF21B) in non-small cell lung cancer (NSCLC). Methods: KIF21B expression in 72 cases of NSCLC tissues was measured by immunohistochemical staining (IHC). We used shRNA-KIF21B interference to silence KIF21B in NSCLC H1299 and A549 cells and normal lung epithelial bronchus BEAS-2B cells. The biological roles of KIF21B in the growth and metastasis abilities of NSCLC cells were measured by Cell Counting Kit-8 (CCK8), colony formation and Hoechst 33342/PI, wound-healing, and Transwell assays, respectively. Expression of apoptosis-related proteins was determined using western blot. The effect of KIF21B on tumor growth in vivo was examined using nude mice model. Results: KIF21B was up-regulated in NSCLC tissues, and correlated with pathological lymph node and pTNM stage, its high expression was predicted a poor prognosis of patients with NSCLC. Silencing of KIF21B mediated by lentivirus-delivered shRNA significantly inhibited the proliferation ability of H1299 and A549 cells. KIF21B knockdown increased apoptosis in H1299 and A549 cells, down-regulated the expression of Bcl-2 and up-regulated the expression of Bax and active Caspase 3. Moreover, KIF21B knockdown decreased the level of phosphorylated form of Akt (p-Akt) and Cyclin D1 expression in H1299 and A549 cells. In addition, silencing of KIF21B impeded the migration and invasion of H1299 and A549 cells. Further, silencing of KIF 21B dramatically inhibited xenograft growth in BALB/c nude mice. However, silencing of KIF21B did not affect the proliferation, migration and invasion of BEAS-2B cells.Conclusions: These results reveal that KIF21B is up-regulated in NSCLC and acts as an oncogene in the growth and metastasis of NSCLC, which may function as a potential therapeutic target and a prognostic biomarker for NSCLC.

Overexpression of Calcium Activated Chloride Channel A4 Suppressed the Proliferation, Invasion and Gemcitabine Resistance of Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 10 (4) ◽  
pp. 435-442
Author(s):  
Ruowen Zhang ◽  
Aihua Ren ◽  
Zhaohui Wang ◽  
Dawei Wang
Keyword(s):  
Lung Cancer ◽  
Wound Healing ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Small Cell Lung

Lung cancer is one kind of the malignant tumor with high mortality. And non-small cell lung cancer is the main subtype of lung cancer. And the proteins of CLCA family (CLCA1, CLCA2 and CLCA4) played an inhibitory role in the occurrence and development of multiple types of tumors. However, the effect of CLCA4 on non-small cell lung cancer cells remains unclear. In our study, we used the lentivirus to establish the overexpressed CLCA4 A549 cells. Next, the CCK-8 and clone formation assays were performed to detect the changes of proliferation of A549 cells. The wound healing and transwell assays were performed to determine the changing of the migration and invasion of A549 cells. Then gemcitabine was used to treat these cells and the CCK-8, wound healing and transwell assays were carried out to detect the effect of the combination of gemcitabine and the overexpression of CLCA4 on the proliferation, migration and invasion of A549 cells. After the overexpression of CLCA4, the clone formation and mobility of A549 cells was enhanced. Furthermore, the overexpression of CLCA4 induced the apoptosis of A549 cells and promoted the expression of apoptosis related proteins. The combination of gemcitabine and the overexpression of CLCA4 further suppressed the proliferation, migration and invasion of A549 cells. CLCA4 inhibited the proliferation, migration and invasion of non-small cell lung cancer cells. CLCA4 also strengthened the sensitivity of non-small cell lung cancer cells for gemcitabine.

scholarly journals Overexpression of miR-758 inhibited proliferation, migration, invasion, and promoted apoptosis of non-small cell lung cancer cells by negatively regulating HMGB

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Guo-Hua Zhou ◽  
Yi-Yu Lu ◽  
Jing-Lian Xie ◽  
Zi-Kun Gao ◽  
Xiao-Bo Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Luciferase Reporter Gene ◽  
Gene Assay

Abstract Non-small cell lung cancer (NSCLC) is one of the most fatal types of cancer with significant mortality and morbidity worldwide. MicroRNAs (miRs) have been confirmed to have positive functions in NSCLC. In the present study, we try to explore the role of miR-758 in proliferation, migration, invasion, and apoptosis of NSCLC cells by regulating high-mobility group box (HMGB) 3 (HMGB3.) NSCLC and adjacent tissues were collected. Reverse transcription quantitative PCR (RT-qPCR) was employed to detect expression of miR-758 and HMGB3 in NSCLC and adjacent tissues, in BEAS-2B cells and NSCLC cell lines. The targetted relationship between miR-758 and HMGB3 was identified by dual luciferase reporter gene assay. The effects of miR-758 on proliferation, migration, invasion, cell cycle, and apoptosis of A549 cells. MiR-758 expression was lower in NSCLC tissues, which was opposite to HMGB3 expression. The results also demonstrated that miR-758 can target HMGB3. The cells transfected with miR-758 mimic had decreased HMGB3 expression, proliferation, migration, and invasion, with more arrested cells in G1 phase and increased apoptosis. Our results supported that the overexpression of miR-758 inhibits proliferation, migration, and invasion, and promotes apoptosis of NSCLC cells by negative regulating HMGB2. The present study may provide a novel target for NSCLC treatment.

scholarly journals Silencing of PRDX2 Inhibits the Proliferation and Invasion of Non-Small Cell Lung Cancer Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xu Jing ◽  
Lutao Du ◽  
Aijun Niu ◽  
Yunshan Wang ◽  
Yuli Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Lung Epithelial Cells ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung

Peroxiredoxin 2 (PRDX2), a member of the peroxiredoxin family of antioxidant enzymes, has been revealed to be an important player in cancer progression. However, the biological role of PRDX2 in the progression of non-small cell lung cancer (NSCLC) is poor reported. In the present study, the loss-of-function experiments were performed to investigate the specific role of PRDX2 in the growth and invasion of NSCLC. The results revealed that knockdown of PRDX2 by siRNA interference significantly suppressed the proliferation, migration, and invasion of A549 and H1299 cells, as well as diminished the activity of MMP9. Additionally, the decrease in PRDX2 expression significantly promoted apoptosis in NSCLC cells by downregulating expression of Bcl-2 and upregulating the expression of Bax, cleaved caspase 3 and cleaved caspase 9, but had no significant effect on the apoptosis of normal lung epithelial cells BEAS-2B. Moreover, PRDX2 inhibitor also inhibited the proliferation, migration, and invasion of A549 cells and promoted apoptosis. Further, our data demonstrated that silencing of PRDX2 markedly reduced the phosphorylation of Akt and mTOR and expression of downstream proteins Cyclin D1 and p70S6k. In conclusion, our findings indicate that PRDX2 exerts a prooncogenic role in the progression of NSCLC and might be a potential therapeutic target for NSCLC treatment.

scholarly journals miR-598 Represses Cell Migration and Invasion of Non-Small-Cell Lung Cancer by Inhibiting MSI2

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Junbin Guo ◽  
Tairan Liu ◽  
Meiyun Su ◽  
Qingxian Yan
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Target Gene ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Non-small-cell lung cancer (NSCLC) is one of the most frequent solid tumors and regarded as a significant threat to individual health around the world. MicroRNAs (miRs) are recognized as critical governors of gene expression during carcinogenesis, while their clinical significance and mechanism in NSCLC occurrence and development are required for further investigation. In this report, we characterized the functional role of miR-598 and its regulation mechanism in NSCLC. The expression level of miR-598 in NSCLC tissues and cell lines was detected by qRT-PCR. A549 cells were transiently transfected with miR-598 mimics or miR-598 inhibitors. Scratch assay and Transwell assay were used to detect cell transfection, migration, and invasion. Possible binding sites of miR-598 in MSI2 mRNA were predicted by bioinformatics and validated by dual-luciferase reporter gene system. The ability of migration and invasion was examined on cells transfected with MSI2 alone or cotransfected A549 cells with miR-598. The expression of miR-598 in NSCLC tissues was significantly lower than that in adjacent tissues, and the expression of miR-598 in NSCLC cell lines (A549, H1650, and H1299) was also significantly lower than that of normal lung epithelial cell line BEAS-2B. A549 cells were significantly inhibited in migration and invasion after transfection with miR-598 mimics, while miR-598 inhibitors were significantly enhanced in migration and invasion. MSI2 was a direct target gene of miR-598. MSI2 can promote the migration and invasion of A549 cells, but the ability to promote cell migration and invasion was reversed when miR-598 was introduced. In conclusion, miR-598 inhibits the migration and invasion of NSCLC by downregulating the target gene MSI2.

scholarly journals Metformin mediated microRNA-7 upregulation inhibits growth, migration, and invasion of non-small cell lung cancer A549 cells

2020 ◽  
Vol 31 (4) ◽  
pp. 345-352 ◽  
Author(s):  
Jingying Dong ◽  
Heng Peng ◽  
Xiaolong Yang ◽  
Wenbing Wu ◽  
Yanan Zhao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

scholarly journals LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Juan Ma ◽  
Haiyan Miao ◽  
Haiyun Zhang ◽  
Jingjing Ren ◽  
Shengyan Qu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Regulatory Function ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Luciferase Reporter Gene

Abstract Background Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear. Methods GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot. Results GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p. Conclusions GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.

scholarly journals Long Noncoding RNA MLK7-AS1 Promotes Non-Small-Cell Lung Cancer Migration and Invasion via the miR-375-3p/YWHAZ Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Jingzhou Jia ◽  
Jiwei Sun ◽  
Wenbo Wang ◽  
Hongmei Yong
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
A549 Cells ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Cell Migration And Invasion

Long noncoding RNAs act essential regulators in lung cancer tumorigenesis. Our research aimed to investigate the potential function and molecular mechanisms of MLK7-AS1 in NSCLC (non-small-cell lung cancer). QRT-PCR results indicated that the MLK7-AS1 expression level was upregulated in NSCLC cells and tissues. MLK7-AS1 strengthened cell migration and invasion in H1299 and A549 cells. Luciferase reporter assay found that MLK7-AS1 functioned as an endogenous sponge for miR-375-3p. Transwell assay results showed that miR-375-3p suppressed cell migration and invasion in H1299 and A549 cells. YWHAZ was confirmed as a target gene of miR-375-3p by Targetscan. YWHAZ overexpression promoted the invasion of H1299 and A549 cells. MLK7-AS1 upregulated YWHAZ expression and enhanced H1299 and A549 cell invasion by sponging miR-375-3p. MLK7-AS1 improved the metastasis ability of A549 in vivo. In conclusion, MLK7-AS1 was identified as a novel oncogenic RNA in NSCLC and can function as a potential therapeutic target for NSCLC treatment.

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