scholarly journals Differential Effects of WRAP53 Transcript Variants on the Biological Behaviours of Human Non-Small Cell Lung Cancer Cells

2021 ◽  
Author(s):  
Yan Zhu ◽  
Wenjie Sun ◽  
Xueping Jiang ◽  
Rui Bai ◽  
Yuan Luo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
A549 Cell ◽  
Colony Formation ◽  
A549 Cells ◽  
Small Cell ◽  
G1 Phase ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Transcript Variants

Abstract Background: The WD40-encoding RNA antisense to p53 (WRAP53) gene, an antisense gene of TP53, has 3 different transcriptional start sites that yield 3 transcript variants. One of these variants WRAP53-1β encodes a WD repeat-containing protein WRAP53β, whereas WRAP53-1α is a noncoding RNA that regulates p53 mRNA levels. These variants are involved in the progression of non-small cell lung cancer (NSCLC). However, how the different transcript variants regulate NSCLC cell behaviours is to be elucidated.Methods: Wild-type p53 NSCLC A549 cells and p53-mutated H1975 cells were transfected with WRAP53-1α and WRAP53-1β siRNAs, and their behaviours were examined colony formation, cell viability, apoptosis, cell cycle, wound healing, and cell invasion assays.Results: WRAP53-1α knockdown increased the mRNA and protein levels of p53, whereas depletion of WRAP53-1β had no effect on p53 expression. WRAP53-1α knockdown suppressed colony formation and proliferation of A549 cells, but had the opposite effects on H1975 cells. However, WRAP53-1β knockdown promoted A549 cell growth. Depletion of WRAP53-1α and WRAP53-1β promoted apoptosis in A549 but not H1975 cells. WRAP53-1α knockdown increased the proportion of A549 but not H1975 cells at the G0/G1 phase. However, WRAP53-1β knockdown decreased the proportion of cells at the G0/G1 phase in A549 cells. Depletion of WRAP53-1α suppressed A549 cell migration and invasion, and promoted H1975 cell migration and invasion. However, depletion of WRAP53-1β had the opposite effects.Conclusions: The 2 WRAP53 transcript variants exerted opposite functions in NSCLC cells and regulated NSCLC cell behaviours in a p53-dependent manner.

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 Curcumin inhibits migration and invasion of non-small cell lung cancer cells through up-regulation of miR-206 and suppression of PI3K/AKT/mTOR signaling pathway

2020 ◽  
Vol 70 (3) ◽  
pp. 399-409 ◽  
Author(s):  
Naizhi Wang ◽  
Tao Feng ◽  
Xiaona Liu ◽  
Qin Liu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
A549 Cells ◽  
Small Cell ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Inhibitory Effects ◽  
Small Cell Lung ◽  
Phosphorylation Level

AbstractCurcumin has been proved to inhibit cell proliferation and induce cell apoptosis in non-small cell lung cancer (NSCLC). However, little is known about antimetastatic effects and molecular mechanisms of curcumin in NSCLC. In this study, we investigated the involvement of miR-206 in curcumin’s anti-invasion and anti-migration in NSCLC. Cell proliferation was determined by MTT assay. Cell migration and invasion were analyzed by wound healing assay and transwell assay. MiRNA-206 expression was detected by real-time PCR. Western blot was used to detect the protein expression of PI3K/AKT/mTOR signaling pathway. Curcumin significantly inhibited migration and invasion in A549 cells, accompanied by significantly elevated miR-206 expression. Overexpression of miR-206 could inhibit migration and invasion of A549 cells, but it could also significantly decrease the phosphorylation levels of mTOR and AKT. The inhibition of miR-206 promoted cell migration, invasion and increased the phosphorylation level of mTOR and AKT. Furthermore, miR-206 mimics improved the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT in A549 cells. On the contrary, MiR-206 inhibitors reversed the inhibitory effects of curcumin on cell migration, invasion and the phosphorylation level of mTOR and AKT. In conclusion, curcumin inhibited cell invasion and migration in NSCLC by elevating the expression of miR-206 which further suppressed the activation of the PI3K/AKT/mTOR pathway.

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.

scholarly journals Erianthridin suppresses non-small-cell lung cancer cell metastasis through inhibition of Akt/mTOR/p70S6K signaling pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sutthaorn Pothongsrisit ◽  
Kuntarat Arunrungvichian ◽  
Yoshihiro Hayakawa ◽  
Boonchoo Sritularak ◽  
Supachoke Mangmool ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Protein Kinase ◽  
Small Cell Lung Cancer ◽  
Cancer Metastasis ◽  
Small Cell ◽  
Migration And Invasion ◽  
Lung Cancer Cell ◽  
Small Cell Lung ◽  
Cell Metastasis

AbstractCancer metastasis is a major cause of the high mortality rate in lung cancer patients. The cytoskeletal rearrangement and degradation of extracellular matrix are required to facilitate cell migration and invasion and the suppression of these behaviors is an intriguing approach to minimize cancer metastasis. Even though Erianthridin (ETD), a phenolic compound isolated from the Thai orchid Dendrobium formosum exhibits various biological activities, the molecular mechanism of ETD for anti-cancer activity is unclear. In this study, we found that noncytotoxic concentrations of ETD (≤ 50 μM) were able to significantly inhibit cell migration and invasion via disruption of actin stress fibers and lamellipodia formation. The expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 was markedly downregulated in a dose-dependent manner after ETD treatment. Mechanistic studies revealed that protein kinase B (Akt) and its downstream effectors mammalian target of rapamycin (mTOR) and p70 S6 kinase (p70S6K) were strongly attenuated. An in silico study further demonstrated that ETD binds to the protein kinase domain of Akt with both hydrogen bonding and van der Waals interactions. In addition, an in vivo tail vein injection metastasis study demonstrated a significant effect of ETD on the suppression of lung cancer cell metastasis. This study provides preclinical information regarding ETD, which exhibits promising antimetastatic activity against non-small-cell lung cancer through Akt/mTOR/p70S6K-induced actin reorganization and MMPs expression.

scholarly journals Ovalitenone Inhibits the Migration of Lung Cancer Cells via the Suppression of AKT/mTOR and Epithelial-to-Mesenchymal Transition

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 638
Author(s):  
Kittipong Sanookpan ◽  
Nongyao Nonpanya ◽  
Boonchoo Sritularak ◽  
Pithi Chanvorachote
Keyword(s):  
Lung Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Colony Formation ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition

Cancer metastasis is the major cause of about 90% of cancer deaths. As epithelial-to-mesenchymal transition (EMT) is known for potentiating metastasis, this study aimed to elucidate the effect of ovalitenone on the suppression of EMT and metastasis-related behaviors, including cell movement and growth under detached conditions, and cancer stem cells (CSCs), of lung cancer cells. Methods: Cell viability and cell proliferation were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazo-liumbromide (MTT) and colony formation assays. Cell migration and invasion were analyzed using a wound-healing assay and Boyden chamber assay, respectively. Anchorage-independent cell growth was determined. Cell protrusions (filopodia) were detected by phalloidin-rhodamine staining. Cancer stem cell phenotypes were assessed by spheroid formation. The proteins involved in cell migration and EMT were evaluated by Western blot analysis and immunofluorescence staining. Results: Ovalitenone was used at concentrations of 0–200 μM. While it caused no cytotoxic effects on lung cancer H460 and A549 cells, ovalitenone significantly suppressed anchorage-independent growth, CSC-like phenotypes, colony formation, and the ability of the cancer to migrate and invade cells. The anti-migration activity was confirmed by the reduction of filopodia in the cells treated with ovalitenone. Interestingly, we found that ovalitenone could significantly decrease the levels of N-cadherin, snail, and slug, while it increased E-cadherin, indicating EMT suppression. Additionally, the regulatory signaling of focal adhesion kinase (FAK), ATP-dependent tyrosine kinase (AKT), the mammalian target of rapamycin (mTOR), and cell division cycle 42 (Cdc42) was suppressed by ovalitenone. Conclusions: The results suggest that ovalitenone suppresses EMT via suppression of the AKT/mTOR signaling pathway. In addition, ovalitenone exhibited potential for the suppression of CSC phenotypes. These data reveal the anti-metastasis potential of the compound and support the development of ovalitenone treatment for lung cancer therapy.

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.

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