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Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer.


ABSTRACT:

Objective

To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes.

Methods

To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting dilution monoclone assay. We then analyzed those genes' biological activities by knocking down their expression in SPC-A-1sci cells using siRNA and lenti-viral shRNA vectors, followed by determinations of the invasion and migration capabilities of the resulting cell lines in vitro as well as their potential for inducing occurrence and metastasis of lung cancer in vivo. To examine the clinical relevance of these findings, we analyzed the expression levels of the identified genes in human lung cancer tissues (n?=?135) and matched adjacent normal tissues by immunohistochemical (IHC) staining.

Results

Three monoclonal cell strains characterized with high, medium or low metastatic abilities were successfully selected. Gene array and bioinformatics analyses implied that osteopontin, LAMB3 and ITGB1 were key genes involved in lung cancer. Knockdown of these genes suppressed human lung cancer cell invasion and metastasis in vitro and in vivo. Clinical sample analyses indicated that osteopontin, LAMB3 and ITGB1 protein expression levels were higher in lung cancer patients, compared to non-cancerous adjacent tissues, and correlated with lymphatic metastasis.

Conclusions

We confirmed that osteopontin, LAMB3 and ITGB1 played important roles in the occurrence and metastasis of lung cancer, thus provided important clues to understanding the molecular mechanism of metastasis and contributing to the therapeutic treatment of lung cancer.

SUBMITTER: Wang XM 

PROVIDER: S-EPMC3575388 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Integrative analyses identify osteopontin, LAMB3 and ITGB1 as critical pro-metastatic genes for lung cancer.

Wang Xiao-Min XM   Li Jing J   Yan Ming-Xia MX   Liu Lei L   Jia De-Shui DS   Geng Qin Q   Lin He-Chun HC   He Xiang-Huo XH   Li Jin-Jun JJ   Yao Ming M  

PloS one 20130218 2


<h4>Objective</h4>To explore the key regulatory genes associated with lung cancer in order to reduce its occurrence and progress through silencing these key genes.<h4>Methods</h4>To identify the key regulatory genes involved in lung cancer, we performed a combination of gene array and bioinformatics analyses to compare gene transcription profiles in 3 monoclonal cell strains with high, medium or low metastatic abilities, which were separated from the SPC-A-1sci and SPC-A-1 cell lines by limiting  ...[more]

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