Abstract
Background MiR-30c-2* is considered to be a tumor suppressor microRNA in various cancers and is associated with gemcitabine sensitivity of lung cancer cells. Downregulation of miR-30c-2* promotes tumor invasion via increased expression of metastasis-associated protein-1. We hypothesized that downregulated expression of miR-30c-2* was involved in human papillomavirus–associated lung tumorigenesis and drug resistance. Methods We examined whether expression of human papillomavirus 16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c-2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by immunohistochemical and real-time polymerase chain reaction analysis. Results Our results showed that miR-30C-2* levels were increased 45-fold in the E6-knockdown TL-1 cells when compared with levels in the parental cells. More interestingly, metastasis-associated protein-1 expression correlated negatively with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression in lung tumors from lung cancer patients. Metastasis-associated protein-1 expression levels in the tumor tissues correlated positively with tumor stage and nodal metastasis. Patients with high metastasis-associated protein-1 expression, and especially patients infected with human papillomavirus, experienced a poor clinical outcome, tumor recurrence, and a poor therapeutic response compared with those with low metastasis-associated protein-1 expression. Conclusion These results showed that miR-30C-2* and levels of downstream metastasis-associated protein-1 gene expression in the tumor tissues of patients could be useful in predicting clinical outcome and therapeutic response and in selecting useful therapeutic drugs for lung cancer patients, especially patients with human papillomavirus infection.
| Original language | English |
|---|---|
| Pages (from-to) | 1591-1598 |
| Number of pages | 8 |
| Journal | Surgery (United States) |
| Volume | 160 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Dec 1 2016 |
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MiR-30c-2* negative regulated MTA-1 expression involved in metastasis and drug resistance of HPV-infected non-small cell lung cancer. / Wu, Yi Liang; Hsu, Nan-Yung; Lin, Frank Cheau Feng; Lee, Huei; Cheng, Ya-Wen.
In: Surgery (United States), Vol. 160, No. 6, 01.12.2016, p. 1591-1598.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - MiR-30c-2* negative regulated MTA-1 expression involved in metastasis and drug resistance of HPV-infected non-small cell lung cancer
AU - Wu, Yi Liang
AU - Hsu, Nan-Yung
AU - Lin, Frank Cheau Feng
AU - Lee, Huei
AU - Cheng, Ya-Wen
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background MiR-30c-2* is considered to be a tumor suppressor microRNA in various cancers and is associated with gemcitabine sensitivity of lung cancer cells. Downregulation of miR-30c-2* promotes tumor invasion via increased expression of metastasis-associated protein-1. We hypothesized that downregulated expression of miR-30c-2* was involved in human papillomavirus–associated lung tumorigenesis and drug resistance. Methods We examined whether expression of human papillomavirus 16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c-2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by immunohistochemical and real-time polymerase chain reaction analysis. Results Our results showed that miR-30C-2* levels were increased 45-fold in the E6-knockdown TL-1 cells when compared with levels in the parental cells. More interestingly, metastasis-associated protein-1 expression correlated negatively with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression in lung tumors from lung cancer patients. Metastasis-associated protein-1 expression levels in the tumor tissues correlated positively with tumor stage and nodal metastasis. Patients with high metastasis-associated protein-1 expression, and especially patients infected with human papillomavirus, experienced a poor clinical outcome, tumor recurrence, and a poor therapeutic response compared with those with low metastasis-associated protein-1 expression. Conclusion These results showed that miR-30C-2* and levels of downstream metastasis-associated protein-1 gene expression in the tumor tissues of patients could be useful in predicting clinical outcome and therapeutic response and in selecting useful therapeutic drugs for lung cancer patients, especially patients with human papillomavirus infection.
AB - Background MiR-30c-2* is considered to be a tumor suppressor microRNA in various cancers and is associated with gemcitabine sensitivity of lung cancer cells. Downregulation of miR-30c-2* promotes tumor invasion via increased expression of metastasis-associated protein-1. We hypothesized that downregulated expression of miR-30c-2* was involved in human papillomavirus–associated lung tumorigenesis and drug resistance. Methods We examined whether expression of human papillomavirus 16/18 oncoprotein and miR-30c-2*-associated genes could be linked to patient outcome by collecting 319 lung tumors from patients with non-small cell lung cancer to determine expression of human papillomavirus 16/18 E6 protein, miR-30c-2*, and miR-30c-2* downstream metastasis-associated protein-1 mRNA by immunohistochemical and real-time polymerase chain reaction analysis. Results Our results showed that miR-30C-2* levels were increased 45-fold in the E6-knockdown TL-1 cells when compared with levels in the parental cells. More interestingly, metastasis-associated protein-1 expression correlated negatively with miR-30C-2* and positively with human papillomavirus 16 E6 protein expression in lung tumors from lung cancer patients. Metastasis-associated protein-1 expression levels in the tumor tissues correlated positively with tumor stage and nodal metastasis. Patients with high metastasis-associated protein-1 expression, and especially patients infected with human papillomavirus, experienced a poor clinical outcome, tumor recurrence, and a poor therapeutic response compared with those with low metastasis-associated protein-1 expression. Conclusion These results showed that miR-30C-2* and levels of downstream metastasis-associated protein-1 gene expression in the tumor tissues of patients could be useful in predicting clinical outcome and therapeutic response and in selecting useful therapeutic drugs for lung cancer patients, especially patients with human papillomavirus infection.
UR - http://www.scopus.com/inward/record.url?scp=84995680648&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84995680648&partnerID=8YFLogxK
U2 - 10.1016/j.surg.2016.06.025
DO - 10.1016/j.surg.2016.06.025
M3 - Article
C2 - 27506865
AN - SCOPUS:84995680648
VL - 160
SP - 1591
EP - 1598
JO - Surgery
JF - Surgery
SN - 0039-6060
IS - 6
ER -