LASP-1, regulated by miR-203, promotes tumor proliferation and aggressiveness in human non-small cell lung cancer

Zheng, Jie; Wang, Fangping; Lu, Shaoying; Wang, Xinbo

doi:10.1016/j.yexmp.2015.11.031

Cited by 23 publications

(41 citation statements)

References 27 publications

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“…In cancer, miRNAs play an important role in cell proliferation, invasion and apoptosis and may influence DDP resistance (9)(10)(11). Various surveys suggest that miR-203 exhibits abnormal expression in tumor tissues and takes part in the regulation of proliferation, invasion, metastasis and prognosis of tumor cells (12)(13)(14)(15)(16)(17)(18). miR-203 has shown potential in the modulation of DDP sensitivity of human cancer cells (9,(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Cheng

Zhang

et al. 2017

Oncology Reports

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The number of new lung cancer cases diagnosed yearly is high, and the mortality rate has not substantially declined. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and adenocarcinoma accounts for the largest proportion of NSCLC. Currently, platinum-based combined chemotherapy, particularly cisplatin (DDP) is still the main form of treatment for advanced NSCLC. However, cisplatin resistance often occurs in patients who receive chemotherapy. Previous studies offer various explanations for how miRNAs affect cisplatin resistance, but the underlying mechanism remains largely unknown. The present study was designed to focus on miR-203 and Dickkopf-1 (DKK1), investigating the potential mechanisms involved in cisplatin resistance in tissues of lung adenocarcinoma and A549/H460 cell lines. In DDP-sensitive NSCLC samples, miR-203 was expressed at a higher level when compared with this level in DDP-insensitive samples, while DKK1 mRNA was expressed at a relatively low level as indicated by qRT-PCR. Dual luciferase reporter assay revealed that DKK1 is a target gene of miR-203 in A549 and H460 cells. Upregulation of miR-203 reduced the IC50 value of cisplatin in the A549 and H460 cells by inhibiting cell growth and promoting cell apoptosis. Similar effects of tumor inhibition and cisplatin sensitization were verified in vivo. Further research showed that both overexpression of miR-203 and knockdown of DKK1 increased the sensitization to DDP with a lower IC50 value. Upon DKK1 knockdown, overexpression of miR-203 had no added effects on the sensitivity of the cells. In addition, miR-203 was unable to sensitize cells with DKK1 that lacked the 3' untranslated region (3'UTR). We conclude that miR-203 targets the 3'UTR of DKK1, and increases cisplatin sensitivity in A549/H460 cell lines.

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Section: Introductionmentioning

confidence: 99%

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Cheng

Zhang

et al. 2017

Oncology Reports

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“…Our data showed that endogenous Lasp2 was localized in cytoplasm of NSCLC cells. Interestingly, endogenous Lasp1 was also expressed in the cytoplasm of multiple human cancers including NSCLC . The difference between previous studies and ours may due to different cell types, antibodies, and target proteins.…”

Section: Discussioncontrasting

confidence: 72%

“…The difference between previous studies and ours may due to different cell types, antibodies, and target proteins. Futhermore, in previous studies, overexpression of Lasp1 was identified as a prognositic factor of patients’ adverse survival in a number of cancer entities, including breast cancer, colorectal cancer, gastric cancer, hepatocellular cancer, lung cancer . For the first time, our study indicated that Lasp2 positive expression significantly correlated with histological type, advanced TNM stage, positive lymph node metastasis and predicted poor survival of NSCLC patients.…”

Section: Discussionsupporting

confidence: 51%

Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non‐small cell lung cancer patients

Zhang

Cai

Zhou

et al. 2017

Molecular Carcinogenesis

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Lasp2, as well as Lasp1, is a member of the LIM-protein subfamily of the nebulin group characterized by the combined presence of LIM and SH3 domains. Lasp1 and Lasp2 are highly conserved in their LIM, nebulin-like, and SH3 domains but differ significantly at their linker regions. Lasp1 had been described as an oncogenic protein that was highly expressed in diverse cancer types and facilitated tumor proliferation, invasion, and metastasis process. However, unlike Lasp1, little is known about the functions of Lasp2. In the present study, using immunohistochemistry, we found that Lasp2 expression was significantly correlated with histological type (P = 0.012), advanced TNM stage (P = 0.024), positive regional lymph node metastasis (P = 0.035), and poor overall survival (P = 0.001). Would healing assay and transwell assay results indicated that Lasp2 promoted tumor migration and invasion in NSCLC cells. Furthermore, Lasp2 facilitated Snail expression and inhibited Zo-1. The levels of phosphorylated FAK (Tyr397 and Tyr925) were obviously increased after overexpressing Lasp2 and were downregulated by transfecting Lasp2-siRNA. FAK inhibitor counteracted upregulating Snail expression and downregulating of Zo-1 expression induced by Lasp2 overexpression. Taken together, Lasp2 may facilitate tumor migration and invasion of NSCLCs through FAK-Snail/Zo-1 signaling pathway. Lasp2 may be a potential prognostic predictor of NSCLC patients.

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“…Studies have demonstrated that LASP-1 was notably upregulated and promoted tumor proliferation, invasion and metastasis in multiple malignant tumors, including NSCLC. LASP-1 was reported to be regulated by miR-203 and facilitate tumor proliferation and aggressiveness in human NSCLC [ 19 ]. LASP-1 was also reported to promote the malignant phenotype of NSCLC via inducing phosphorylation of the FAK-AKT pathway [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

“…LIM and SH3 domain protein 1 (LASP1) is a potential negative predictor of NSCLC [ 18 ]. It has been proved to be the down-stream factor of miR-203 [ 19 ] and miR-29a [ 20 ] in the suppression or proliferation of human NSCLC. Therefore, this study was carried out to investigate the associations among lncRNA LINC01503, miR-342-3p, and LASP1 in the development and progression of NSCLC.…”

Section: Introductionmentioning

confidence: 99%

LINC01503/miR-342-3p facilitates malignancy in non-small-cell lung cancer cells via regulating LASP1

Shen

Sun

2020

Respir Res

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Background Non-small cell lung cancer (NSCLC) is one of the major types of lung cancer, which is a prevalent human disease all over the world. LncRNA LINC01503 is a super-enhancer-driven long non-coding RNA that is dysregulated in several types of human cancer. However, its role in NSCLC remains unknown. Methods Thirty NSCLC patients were recruited between April 2012 and April 2016. Luciferase reporter assay, qRT-PCR, Cell Counting Kit-8 (CCK-8), Transwell migration assay, RNA pull-down assay, western blotting, 5-ethynyl-29-deoxyuridine (EdU) assays, and flow cytometry were utilized to characterize the roles and relationships among LINC01503, miR-342-3p, and LASP1 in NSCLC. The transplanted mouse model was built to examine their biological functions in vivo. Results We demonstrated that the expression of lncRNA LINC01503 and LIM and SH3 domain protein 1 (LASP1) were upregulated and miR-342-3p was downregulated in NSCLC samples and cell lines. Functional experiments revealed that inhibiting the expression of LINC01503 or over-expression of miR-342-3p inhibited NSCLC growth and metastasis both in vitro and in vivo. In addition, LINC01503 could bind to miR-342-3p and affect the expression of LASP1. Conclusion These results provide a comprehensive analysis of the roles of LINC01503 as a competing endogenous RNA (ceRNA) in NSCLC progression.

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LASP-1, regulated by miR-203, promotes tumor proliferation and aggressiveness in human non-small cell lung cancer

Cited by 23 publications

References 27 publications

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Overexpression of miR-203 increases the sensitivity of NSCLC A549/H460 cell lines to cisplatin by targeting Dickkopf-1

Lasp2 enhances tumor invasion via facilitating phosphorylation of FAK and predicts poor overall survival of non‐small cell lung cancer patients

LINC01503/miR-342-3p facilitates malignancy in non-small-cell lung cancer cells via regulating LASP1

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