GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion

AbstractEpithelial–mesenchymal transition (EMT) plays a pivotal role for tumor progression. Recent studies have revealed the existence of distinct intermediate states in EMT (partial EMT); however, the mechanisms underlying partial EMT are not fully understood. Here, we demonstrate that αvβ3 integrin induces partial EMT, which is characterized by acquiring mesenchymal phenotypes while retaining epithelial markers. We found αvβ3 integrin to be associated with poor survival in patients with lung adenocarcinoma. Moreover, αvβ3 integrin-induced partial EMT promoted migration, invasion, tumorigenesis, stemness, and metastasis of lung cancer cells in a TGF-β-independent fashion. Additionally, TGF-β1 promoted EMT progression synergistically with αvβ3 integrin, while a TGF-β signaling inhibitor showed no effect on αvβ3 integrin-induced partial EMT. Meanwhile, the microRNA-200 family abolished the αvβ3 integrin-induced partial EMT by suppressing αvβ3 integrin cell surface expression. These findings indicate that αvβ3 integrin is a key inducer of partial EMT, and highlight a new mechanism for cancer progression.

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LINC01089 functions as a ceRNA for miR-152-3p to inhibit non‐small lung cancer progression through regulating PTEN

Cancer Cell International ◽

10.1186/s12935-021-01846-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Huixian Zhang ◽

Hao Zhang ◽

Xingya Li ◽

Siyuan Huang ◽

Qianqian Guo ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Expression Level ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Loss Of Function ◽

Protein Coding ◽

Tensin Homolog ◽

Pten Mrna

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

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