Yi-Liang Wu1, Nan-Yung Hsu2, Frank Cheau-Feng Lin3, Huei Lee4, Ya-Wen Cheng5. 1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan. 2. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; Division of Thoracic Surgery, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China. 3. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan. 4. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. 5. Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan. Electronic address: ywc@tmu.edu.tw.
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.
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 cancerpatients. 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 cancerpatients, especially patients with human papillomavirus infection.
Authors: Joana M O Santos; Sara Peixoto da Silva; Natália R Costa; Rui M Gil da Costa; Rui Medeiros Journal: Cancers (Basel) Date: 2018-12-05 Impact factor: 6.639