Invasive Ability Of Non-small Cell Lung Cancer Cells Research Articles

M2-like macrophage-derived exosomes facilitate metastasis in non-small-cell lung cancer by delivering integrin αVβ3.

Metastasis is the most prevalent cause of cancer deaths, and immunological components of the tumor microenvironment, especially tumor-associated macrophages (TAMs), play a vital role in cancer metastasis. However, the underlying mechanisms of TAMs on non-small-cell lung cancer (NSCLC) metastasis remain largely unexplored. Herein, we demonstrated that M2-like TAMs facilitate the migration and invasion of cancer cells in vitro and in vivo through intercellular delivery of M2-like macrophage-derived exosomes (M2-exos). Importantly, we found that M2-exos had considerably higher levels of integrin (ITG) αV and β3. The impact of M2-like macrophage-mediated invasion and migration of NSCLC cells was clearly decreased when ITG αVβ3 was blocked. Mechanistically, exosomal ITG αVβ3 produced from M2-like macrophages successfully triggered the focal adhesion kinase signaling pathway in recipient cells, boosting the migratory and invasive abilities of NSCLC cells. Clinically, we found that metastatic NSCLC patients had greater ITG αV and β3 expression, which was associated with a worse prognosis. This study reveals a novel mechanism by which M2-exos significantly increased NSCLC cell migration and invasion by delivering integrin αVβ3. Exosomal ITG αVβ3 can be used as a potential prognostic marker, and blocking ITG αVβ3 could be a viable treatment option for preventing tumor metastasis.

Anwuligan inhibits the progression of non-small cell lung cancer via let-7c-3p/PI3K/AKT/mTOR axis.

Anwuligan (ANW) isolated from nutmeg, also known as myristyl lignan, has attracted attention due to its therapeutic potential in diseases. However, its effect on lung cancer is still unclear. In this study, the cytotoxicity of ANW on non-small cell lung cancer (NSCLC) cells was detected using a Cell Counting Kit-8 (CCK-8) assay.In vitro, clone formation, wound healing, and Transwell assays were used to investigate the migratory and invasive abilities of NSCLC cells after ANW treatment. The expression levels of the associated proteins were detected using Western blotting. A luciferase assay was used to validate the binding of let-7c-3p to the 3'-untranslated region (UTR) of PIK3CA. In vivo, an A549 cell xenograft mouse model was used to verify the effect of ANW on tumor growth. The results showed that ANW treatment (20 or 50 μM) had obvious cytotoxicity against A549 and H460 cells, suppressing cell proliferation and migration in vitro. In vivo, the growth of the implanted tumor was inhibited by ANW in a nude mouse model. The growth of NSCLC cells was also inhibited by let-7c-3p overexpression in vitro and in vivo. The inhibitory effect of ANW on the proliferation and metastasis of NSCLC cells was weakened by the downregulation of let-7c-3p, whereas it was enhanced by the overexpression of let-7c-3p; PIK3CA was the main target of let-7c-3p. In summary, ANW inhibits the growth and metastasis of NSCLC cells in vivo and in vitro by upregulating the expression of let-7c-3p, which can regulate the PI3K/AKT/mTOR signaling pathway. PIK3CA is the main target of let-7c-3p.

MicroRNA‑671‑5p inhibits cell proliferation, migration and invasion in non‑small cell lung cancer by targeting MFAP3L.

MicroRNA (miR)-671-5p serves as a tumor suppressor in several types of cancer, including gastric and breast cancer. However, the function of miR-671-5p in non-small cell lung cancer (NSCLC) has not been described in detail. The present study aimed to investigate the role of miR-671-5p in NSCLC. The expression levels of miR-671-5p were determined in NSCLC tissue samples and cell lines using reverse transcription-quantitative PCR. Prediction of miR-671-5p targets was performed using the TargetScan database and verified by luciferase reporter assay and western blot analysis. Functional experiments, including Cell Counting Kit-8, wound healing and Transwell assays, were performed in NSCLC cells. The results of the present study demonstrated that lower expression levels of miR-671-5p were observed in NSCLC tissues and cell lines compared with those in the corresponding controls. Low miR-671-5p levels were significantly associated with an advanced Tumor-Node-Metastasis stage and lymph node metastasis in patients with NSCLC. Microfibril-associated protein 3-like (MFAP3L) was confirmed to be a direct target of miR-671-5p. The proliferative, migratory and invasive abilities of NSCLC cells were suppressed following transfection with miR-671-5p mimics and promoted by the miR-671-5p inhibitor compared with those in the respective control groups. In addition, the effects of miR-671-5p on cell proliferation, migration and invasion, as well as the expression levels of proliferating cell nuclear antigen, E-cadherin, N-cadherin and vimentin were reversed by MFAP3L overexpression. In conclusion, targeting the miR-671-5p/MFAP3L signaling pathway may be a promising therapeutic strategy for NSCLC treatment.

Inhibin βA is an independent prognostic factor that promotes invasion via Hippo signaling in non‑small cell lung cancer.

Inhibin βA (INHBA) serves a prognostic and tumor-promoting role in numerous types of cancer. The present study aimed to determine the clinical significance of INHBA in non-small cell lung cancer (NSCLC) and the mechanisms underlying its potential tumor-promoting effect. INHBA expression was detected in clinical NSCLC samples using immunohistochemistry. In vivo loss- and gain-of-function studies were performed to determine the effects of INHBA on NSCLC invasion. In addition, protein and mRNA expression levels of INHBA, yes-associated protein (YAP), large tumor suppressor 1/2 kinase (LATS1/2), connective tissue growth factor, cysteine rich angiogenic inducer 61 and Merlin were assessed using western blotting and reverse transcription-quantitative PCR, respectively, to investigate the mechanism by which INHBA may affect the invasion of NSCLC. The present study revealed that INHBA was significantly upregulated in 238 clinical NSCLC samples compared with its expression levels in paired adjacent non-cancerous tissues, and in metastatic nodules compared with in primary tumors. Notably, high INHBA expression was statistically associated with clinicopathological features, including poor differentiation and advanced tumor stage. INHBA positivity was statistically related to decreased 5-year overall survival, for which INHBA was an independent prognostic factor. Furthermore, INHBA promoted NSCLC invasion in vitro. In NSCLC, INHBA expression was associated with the nuclear levels of YAP and INHBA overexpression enhanced the invasive abilities of NSCLC cells via inhibiting the Hippo pathway. Mechanistically, INHBA inhibited l LATS1/2 phosphorylation and induced YAP nuclear translocation by downregulating the protein expression levels of Merlin. In conclusion, INHBA may negatively regulate the Hippo pathway to act as a tumor promotor, and could represent a marker of prognosis in NSCLC.

ROR1-AS1 knockdown inhibits growth and invasion and promotes apoptosis in NSCLC cells by suppression of the PI3K/Akt/mTOR pathway.

The role of ROR1-AS1 in non-small-cell lung cancer (NSCLC) remains unclear. Therefore, we aimed to investigate the functional role of ROR1-AS1 in NSCLC and to explore the underlying mechanisms. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay was performed to detect cell proliferation. Transwell assay was performed to evaluate cell invasive ability. Cell apoptotic rates and caspase-3/7 activity were determined to evaluate apoptosis. The expression levels of PI3K/Akt/mTOR pathway-related proteins were measured using Western blot analysis. Results showed that ROR1-AS1 expression was upregulated in NSCLC samples. Knockdown of ROR1-AS1 inhibited the viability and invasive ability of NSCLC cells. Knockdown of ROR1-AS1 induced apoptotic rate and caspase-3/7 activity and suppressed xenograft NSCLC tumor growth. In addition, ROR1-AS1 knockdown inhibited the activation of the PI3K/Akt/mTOR pathway in NSCLC cells. However, treatment with 740Y-P prevented the effects of si-ROR1-AS1 on viability, invasive ability, and apoptosis of NSCLC cells. These findings implied that ROR1-AS1 playedan oncogenic role in NSCLC via regulating the PI3K/Akt/mTOR pathway.

Long Non-coding RNA snaR Promotes Proliferationin EGFR Wild Type Non-Small Cell Lung Cancer Cells.

Lung cancer is the second most common cancer and has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Over-expression of epidermal growth factor receptor (EGFR) has been clarified in different cancers, and has been shown to have a crucial role in tumor progression. In this study, we evaluated long non-coding RNA small NF90-associated RNA (snaR) expression in different EGFR-statue cell lines. Knockdown experiments were conducted to analyze snaR expression in selected cell lines. MTT and transwell assays were respectively employed to evaluate the proliferative and invasive abilities of NSCLC cells. The expression of snaR was remarkably up-regulated in SPC-A1 and A549 wild-type EGFR cell lines. Down regulation of snaR with small interfering RNA significantly inhibited cell invasion as well as proliferation of SPC-A1 and A549 cells. Our results indicate that snaR may be a potential therapeutic biomarker for NSCLC.

Mannose shows antitumour properties against lung cancer via inhibiting proliferation, promoting cisplatin‑mediated apoptosis and reducing metastasis.

It has been reported that mannose exerts antitumour effects against certain types of cancer. The present study was designed to evaluate whether mannose exerted potential anticancer effects on A549 and H1299 non-small cell lung cancer (NSCLC) cells in vitro, which has not been reported previously. A Cell Counting Kit-8 cell viability assay was used to assess the antiproliferative effects of mannose on NSCLC cells. Flow cytometry-based methods were used to evaluate the effects of mannose on the cell cycle distribution and cisplatin-mediated apoptosis of NSCLC cells. Transwell migration and invasion assays were conducted to examine whether mannose could inhibit the invasive abilities of NSCLC cells. The effects of mannose on the PI3K/AKT and ERK signalling pathways were explored through western blot analysis assessing the expression of phosphorylated (p)-AKT and p-ERK1/2. It was found that mannose showed potential anticancer effects against NSCLC cells in vitro by inhibiting proliferation, inducing G0/G1 cell cycle arrest, promoting cisplatin-induced apoptosis and decreasing the invasive abilities. These data indicate the potential anticancer properties of mannose and suggest the application of mannose-based therapies to treat NSCLC.

LncRNA HANR aggravates the progression of non-small cell lung cancer via mediating miRNA-140-5p.

The aim of this study was to elucidate the function of long non-coding ribonucleic acids (lncRNAs) HANR in aggravating non-small cell lung cancer (NSCLC) progression via targeting microRNA-140-5p (miRNA-140-5p). The relative expression level of HANR in NSCLC tissues and cell lines was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between HANR expression and the prognosis of NSCLC was analyzed. The regulatory effects of HANR on cellular behaviors of NSCLC cells were evaluated by Cell Counting Kit-8 (CCK-8), transwell and wound healing assay. Meanwhile, the relative expression of miRNA-140-5p in NSCLC tissues and cell lines was determined by qRT-PCR. In addition, rescue experiments were carried out to evaluate the potential influence of HANR/miRNA-140-5p on the progression of NSCLC. HANR expression was significantly up-regulated in NSCLC tissues and cell lines. HANR expression was positively correlated with lymphatic metastasis and distant metastasis of NSCLC patients, whereas it was negatively correlated with the overall survival of NSCLC patients. Knockdown of HANR markedly suppressed the proliferative, migratory and invasive abilities of NSCLC cells. In NSCLC tissues, the miRNA-140-5p level was negatively associated with HANR level. Furthermore, inhibited cellular behaviors of NSCLC cells transfected with sh-HANR were partially reversed after miRNA-140-5p knockdown. LncRNA HANR accelerates the proliferative, migratory and invasive abilities of NSCLC via negatively mediating miRNA-140-5p. Furthermore, HANR is closely correlated with lymphatic metastasis, distant metastasis and poor prognosis of NSCLC.

MicroRNA-421 promotes proliferation and invasion of non-small cell lung cancer cells through targeting PDCD4

Recent evidence highlights that microRNAs serve as crucial regulators of tumorigenesis, including non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression profile, clinical significance and biological role of miR-421 in NSCLC. The results showed that miR-421 expression was markedly increased in NSCLC tissues and cell lines. Further experimental data indicated that knockdown of miR-421 significantly inhibited NSCLC cell proliferation and induced cell cycle arrest in vitro. The migratory and invasive abilities of NSCLC cells were also attenuated following miR-421 knockdown. Furthermore, PDCD4 was identified as a direct target of miR-421, and its expression was inversely correlated with miR-421 expression in NSCLC tissues. PDCD4 also abrogated the oncogenic role of miR-421 in NSCLC cells. Collectively, our study revealed that miR-421 is significantly upregulated in NSCLC and might represent a potential therapeutic target for NSCLC patients.

LncRNA FBXL19-AS1 promotes proliferation and metastasis via regulating epithelial-mesenchymal transition in non-small cell lung cancer.

To detect the relative expression of long non-coding ribonucleic acid (lncRNA) F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) in tissues and cells of non-small-cell lung cancer (NSCLC), and investigate the mechanism of lncRNA FBXL19-AS1 in promoting NSCLC cell proliferation and metastasis by regulating epithelial-mesenchymal transition (EMT) via in vitro experiments. The relative expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells was detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The colony formation assay was performed to study the impact of interference with lncRNA FBXL19-AS1 expression on NSCLC cell proliferation. The flow cytometry was applied to determine the influence of si-FBXL19-AS1 on the cycle distribution of NSCLC cells. After the interference with lncRNA FBXL19-AS1 expression, the transwell assay was utilized to measure the changes in the migratory and invasive abilities of NSCLC cells, while the expression changes in EMT-related molecular markers was detected via Western blotting. The results of qRT-PCR showed that the expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells was up-regulated. According to the results of the colony formation assay, the proliferative capacity of NSCLC cells was decreased after the interference with lncRNA FBXL19-AS1 expression. In flow cytometry, it was indicated that the cell cycle was arrested at the G0/G1 phase in the experimental group compared with that in the control group. The transwell assay results showed that the migratory and invasive abilities of NSCLC cells were weakened after the interference with lncRNA FBXL19-AS1 expression. The results of the Western blotting assay revealed that the expressions of EMT-related molecular markers (E-cadherin, N-cadherin, etc.) were changed. The expression of lncRNA FBXL19-AS1 in NSCLC tissues and cells is up-regulated, and the highly expressed lncRNA FBXL19-AS1 can promote NSCLC cell proliferation and metastasis by regulating the EMT.

Long noncoding RNA HOXA-AS2 promotes cell migration and invasion via upregulating IGF-2 in non-small cell lung cancer as an oncogene.

Recent studies have revealed the vital role of long non-coding RNAs (lncRNAs) in tumor progression. This study aims to determine whether lncRNA HOXA-AS2 functions in the metastasis of non-small cell lung cancer (NSCLC). Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was conducted to detect HOXA-AS2 expression in NSCLC tissues. Wound healing assay and transwell assay were performed to evaluate the function of HOXA-AS2 in mediating the behaviors of NSCLC cells. Furthermore, the interaction between IGF2 and HOXA-AS2 in mediating the metastasis of NSCLC was analyzed. By comparing with the expression level in adjacent tissues, HOXA-AS2 expression was higher in NSCLC samples. Moreover, HOXA-AS2 knockdown inhibited invasion and migration of NSCLC cells and, conversely, HOXA-AS2 overexpression obtained the opposite results. In addition, the mRNA and protein expressions of IGF2 were downregulated via HOXA-AS2 knockdown. Besides, the expression of IGF2 was positively correlated to the expression of HOXA-AS2 in NSCLC tissues. In this work, HOXA-AS2 could enhance migratory and invasive abilities of NSCLC cells by upregulating IGF2, which might offer a potential therapeutic target for NSCLC.

Inhibition of miR-24 suppresses malignancy of human non-small cell lung cancer cells by targeting WWOX in vitro and in vivo.

BackgroundWe investigated the effect of micro‐RNA 24 (miR‐24) and WWOX on non‐small cell lung cancer (NSCLC) cell proliferation and migration in vitro and in vivo.MethodsWe performed bioinformatics analysis and 3′ untranslated region luciferase assay to investigate the direct target of miR‐24. Proliferation, apoptosis, and transwell invasion assays were employed to evaluate the effect of WWOX overexpression with pcDNA3‐WWOX and knocking down miR‐24 with miR‐24 small interfering RNA. Quantitative real‐time PCR, Western blot, and immunohistochemistry were also used to investigate miR‐24 and c‐Kit expression, and apoptosis and invasion‐related proteins. Finally, we constructed a tumor xenograft model in nude mice to confirm the effect of miR‐24 on NSCLC cell proliferation in vivo.ResultsAccording to our experimental data, miR‐24 inhibition could induce apoptosis by activating caspase 3 and suppress the viability and proliferation of NSCLC cells in vitro and in vivo. MiR‐24 downregulation could reduce the invasive ability of NSCLC cells by downregulating MMP9. WWOX was identified as a functional target of miR‐24. WWOX overexpression generated the same effect with antagonizing miR‐24, while blocking WWOX counteracted the tumor suppressive effect caused by miR‐24 inhibition. MiR‐24 may function as an oncogene and play an important role in the cell growth and migration of NSCLC.ConclusionsOur findings enhance understanding of the miR‐24 regulatory network and the molecular mechanism that underlies the oncogenesis and development of NSCLC. Suppressing the effect of miR‐24 on cancer cells using a miR‐24 inhibitor may be an attractive therapeutic strategy against NSCLC.

MiR-451a suppressed cell migration and invasion in non-small cell lung cancer through targeting ATF2.

To explore the role of miR-451a in the migration and invasion of non-small cell lung cancer (NSCLC) cells. Quantitative Real time-polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the levels of miR-451a and activating transcription factor 2 (ATF2) in NSCLC. Transwell assay was employed to analyze the migratory and invasive abilities in NSCLC cells. Dual-luciferase reporter assay was applied to confirm the binding condition of miR-451 and its target gene in NSCLC cells. MiR-451a was downregulated in NSCLC tissues and lung cancer cell lines A549 and NCI-H460, while ATF2 was upregulated. The mRNA level of miR-451a was negatively correlated to ATF2. Additionally, miR-451a regulated cell migration and invasion through targeting ATF2. Furthermore, ATF2 could reverse the inhibitory migration and invasion of A549 cells induced by miR-451a. MiR-451a inhibits the migratory and invasive abilities of NSCLC cells through ATF2 regulation. The newly identified miR-451a/ATF2 axis provides a novel insight into the pathogenesis ofNSCLC.

Regulation by Pink1 on the mitochondrial dysfunction in endothelial cells post the hypoxia mimetic agent CoCl2 treatment.

To explore the role of miR-451a in the migration and invasion of non-small cell lung cancer (NSCLC) cells. Quantitative Real time-polymerase chain reaction (qRT-PCR) and Western blot were performed to detect the levels of miR-451a and activating transcription factor 2 (ATF2) in NSCLC. Transwell assay was employed to analyze the migratory and invasive abilities in NSCLC cells. Dual-luciferase reporter assay was applied to confirm the binding condition of miR-451 and its target gene in NSCLC cells. MiR-451a was downregulated in NSCLC tissues and lung cancer cell lines A549 and NCI-H460, while ATF2 was upregulated. The mRNA level of miR-451a was negatively correlated to ATF2. Additionally, miR-451a regulated cell migration and invasion through targeting ATF2. Furthermore, ATF2 could reverse the inhibitory migration and invasion of A549 cells induced by miR-451a. MiR-451a inhibits the migratory and invasive abilities of NSCLC cells through ATF2 regulation. The newly identified miR-451a/ATF2 axis provides a novel insight into the pathogenesis of NSCLC.

Downregulating CD26/DPPIV by apigenin modulates the interplay between Akt and Snail/Slug signaling to restrain metastasis of lung cancer with multiple EGFR statuses

BackgroundMetastasis rather than the primary cancer determines the survival of cancer patients. Activation of Akt plays a critical role in the epithelial-to-mesenchymal transition (EMT), the initial step in lung cancer metastasis. Apigenin (API), a flavonoid with a potent Akt-inhibitory effect, shows oncostatic activities in various cancers. However, the effects of API on metastasis of non-small cell lung cancer (NSCLC) remain unclear.MethodsNSCLC cell lines with different epidermal growth factor receptor (EGFR) statuses and in vivo orthotopic bioluminescent xenograft model were employed to determine antitumor activity of API. Western blot and genetic knockdown by shRNA or genetic overexpression by DNA plasmids were performed to explore the underlying mechanisms. The Cancer Genome Atlas (TCGA) database was used to investigate the prognosis of API-targeted genes.ResultsAPI was demonstrated to inhibit the migration/invasion of NSCLC cells harboring different EGFR statuses via suppressing the Snail/Slug-mediated EMT. Mechanistic investigations showed that CD26/dipeptidyl peptidase IV (DPPIV) was downregulated by API following suppressive interplay of Akt and Snail/Slug signaling to modulate the EMT and the invasive ability of NSCLC cells. CD26 expression was positively correlated with the invasive abilities of NSCLC cells and a worse prognosis of lung cancer patients. Furthermore, we observed that patients with CD26high/Akthigh tumors had the shortest recurrence-free survival times. In vivo, API drastically reduced the growth and metastasis of A549 xenografts through targeting CD26.ConclusionsCD26 may be a useful biomarker for predicting NSCLC progression. API effectively suppressed lung cancer progression by targeting the CD26-Akt-Snail/Slug signaling pathway.

MiR-196b promotes lung cancer cell migration and invasion through the targeting of GATA6.

MicroRNAs (miRNAs) have been proven to regulate gene expression at the protein translation level. miRNA abnormal expression has been associated with the development of lung cancer. In the present study, we aimed to investigate the mechanism of miR-196 in non-small cell lung cancer (NSCLC). The miR-196b and GATA-6 (GATA6) expression levels were examined in NSCLC by RT-qPCR and western blot analysis. Transwell assay was used to assess cell migration and invasion. Moreover, the specific target of miR-196b in NSCLC was verified by the luciferase reporter assay. The expression of miR-196b was higher in both NSCLC tissues and cells than the normal levels. Specifically, the miR-196b mimic group in NSCLC cells markedly promoted cell migration and invasion, while the miR-196b inhibitor group exhibited the opposite effect. Furthermore, GATA6 was verified as a specific target of miR-196b in NSCLC cells and GATA6 could attenuate the migratory and invasive ability of NSCLC cells regulated by miR-196b. In addition, the relationship between GATA6 and miR-196b expression was negatively correlated in NSCLC tissues. Thus, miR-196b enhanced NSCLC cell migration and invasion via the downregulation of GATA6, indicating its potential application in NSCLC diagnosis and therapy.

Matrine suppresses the migration and invasion of NSCLC cells by inhibiting PAX2-induced epithelial-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro. Cell Counting Kit-8 assay was used to evaluate the cell viability. Transwell assay was used to detect the migration and invasion abilities. Microarray assay was used to analyze the differentiated expression genes with or without matrine treatment. Western blotting and real-time polymerase chain reaction were applied to detect the expressions of PAX2, E-cadherin and N-cadherin. Our study showed that matrine could suppress the proliferative activity of NSCLC cells in a dose- and time-dependent manner. Further investigation discovered that the migration and invasion of NSCLC cells were significantly inhibited by treatment with different concentrations of matrine. Microarray assay, real-time polymerase chain reaction and western blotting showed that matrine could significantly decrease the expression of PAX2. In addition, epithelial-mesenchymal transition and related proteins were decreased. In conclusion, matrine may block PAX2 expression to interfere with epithelial-mesenchymal transition signaling pathway that ultimately inhibit the migration and invasion of NSCLC cells in vitro. Matrine might serve as a potential agent for NSCLC treatment.

The long non-coding RNA MIAT regulates zinc finger E-box binding homeobox 1 expression by sponging miR-150 and promoteing cell invasion in non-small-cell lung cancer

The myocardial infarction associated transcript (MIAT), a long non-coding RNA (lncRNA), was originally identified as a candidate gene for myocardial infarction, and was recently shown to participate in the progression of cancer and the process of metastasis. However, the biological role of MIAT and the underlying mechanisms that mediate its role in non-small-cell lung cancer (NSCLC) remain unclear. Here, we have shown that the expression of MIAT in NSCLC tissues was upregulated. Knockdown of MIAT substantially inhibited the invasive ability of NSCLC cells. Moreover, the knockdown of MIAT significantly downregulated the expression of the zinc finger E-box binding homeobox 1 (ZEB1), that was upregulated in NSCLC and that promoted cell invasion. Rather than by direct interactions, we found that MIAT indirectly regulated ZEB1 expression through sponging and suppressing microRNA (miR)-150, which represses ZEB1 and interacts with MIAT in a sequence-specific manner. Thus, MIAT may inhibit ZEB1 expression and promote cell invasion of NSCLC cells via the miR-150/ZEB1 pathway. Taken together, our findings suggested that MIAT plays an oncogenic role in NSCLC through the ZEB1 signaling pathway by sponging miR-150, and MIAT may therefore serve as a valuable prognostic biomarker and therapeutic target for NSCLC.

MicroRNA-199b targets the regulation of ZEB1 expression to inhibit cell proliferation, migration and invasion in non‑small cell lung cancer.

Lung cancer is one of the leading causes of cancer-associated mortality worldwide. Previous evidence suggested that microRNAs (miRs) exhibit important regulatory roles in tumorigenesis and tumor development, including in non‑small cell lung cancer (NSCLC). The present study investigated the expression of miR‑199b in NSCLC tissues and cell lines, in addition to the biological roles of miR‑199b in the carcinogenesis and progression of NSCLC. The results of the present study demonstrated that miR‑199b expression was decreased in NSCLC tissues and cell lines compared with matched adjacent healthy tissues and a healthy human bronchial epithelial cell line, respectively. An MTT assay demonstrated that the viability of NSCLC cells was decreased by miR‑199b. The migratory and invasive abilities of NSCLC cells were suppressed by miR‑199b overexpression. In addition, zinc finger E‑box‑binding homeobox 1 (ZEB1) was identified to be a novel direct downstream and functional target for miR‑199b in NSCLC, using bioinformatics analysis, luciferase reporter assay, the reverse transcription‑quantitative polymerase chain reaction and western blotting. ZEB1 underexpression mimicked the roles of miR‑199b overexpression in NSCLC cells. In conclusion, the present study demonstrated that miR‑199b was downregulated in NSCLC and acted as a tumor suppressor by targeting ZEB1.

LncRNA-PVT1 Facilitates Invasion Through Upregulation of MMP9 in Nonsmall Cell Lung Cancer Cell.

Lung cancer is the most common solid tumor around the world. It has been reported that upregulation of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (lncRNA-PVT1) is closely associated with tumor metastasis. However, the function and underlying molecular mechanism of lncRNA-PVT1 in nonsmall cell lung cancer (NSCLC) invasion remain unknown. In this study, we found that overexpression of lncRNA-PVT1 promoted the invasive ability of NSCLC cells, whereas silence of lncRNA-PVT1 suppressed cell invasion. Furthermore, we found that lncRNA-PVT1 upregulated MMP9 expression in a post-transcriptional manner. Specifically, lncRNA-PVT1 directly interacted with miR-200a and miR-200b, which suppressed MMP9 expression. Taken together, lncRNA-PVT1 functions as a competitive endogenous RNA to regulate MMP9 expression through competitively binding the common microRNAs, miR-200a and miR-200b. These findings suggest that lncRNA-PVT1 could predispose NSCLC patients to metastases and may serve as a promising target for antimetastatic therapies.