Xiufeng Zhang1, Ping Zhao2, Caihong Wang2, Benru Xin3. 1. Department of Pharmacy, People's Hospital of Rizhao, Rizhao, Shandong, PR China. 2. Department of Pharmacy, Rizhao Maternal and Child Health Care Hospital, Rizhao, Shandong, PR China. 3. Department of Pharmacy, People's Hospital of Rizhao, Rizhao, Shandong, PR China. Electronic address: benruxin@outlook.com.
Abstract
BACKGROUND: Due to the poor prognosis and high mortality (over 90%), Pancreas ductal adenocarcinoma (PDAC) is listed as the 7th leading cause of cancer-related death in the world, while gemcitabine sensitivity is key important in PDAC therapy. SNHG14 is thought to be an oncogene in cancer progression. However, the possible role of SNHG14 underlying the progress of the PDAC cell, specifically in gemcitabine resistance remains to be determined. METHODS: We analyzed the PDAC-related data collected from TCGA. PDAC cell line (SW1990) was used as in vitro model. RT-qPCR and western blot were used to detect the autophagy-related gene expression level. MTT and flow cytometry approaches were used to determine cell viability and apoptosis rate. The luciferase reporter assay was used to confirm the direct interaction between SNHG14 and miR-101. The wound healing assay and transwell assay were used to detect the migration and invasion abilities of PDAC cells. RESULTS: The expression of SNHG14 was significantly higher in the PDAC tissues than in the normal tissues, while miR-101 was significantly downregulated in the PDAC tissues. Moreover, the correlation analysis showed that SNHG14 was negatively correlated with miR-101. The in vitro experiments furthermore confirmed their impacts on PDAC cells. Overexpression of SNHG14 and miR-101 inhibitor significantly enhanced cell proliferation, migration, and invasion rate of PDAC cell line. Moreover, SNHG14 knockdown and miR-101 mimics both led to attenuation of gemcitabine resistance-PDAC cell viability and promoted cell apoptosis rate, as well as the reduction of autophagy-related proteins (such as RAB5A and ATG4D). Overexpression of SNHG14 enhanced PDAC cell progression and inhibited cell apoptosis in gemcitabine treatment, as well as the increase of autophagy-related proteins, thus enhanced the chemoresistance of PDAC cells to gemcitabine. CONCLUSIONS: Collectively, we first time revealed that SNHG14 could sponge miR-101 to enhance PDAC cell progression and find the specific axis of SNHG14/miR-101/autophagy underlying the chemoresistance in PDAC cells to gemcitabine, which could promote the progress of PDAC therapy.
BACKGROUND: Due to the poor prognosis and high mortality (over 90%), Pancreas ductal adenocarcinoma (PDAC) is listed as the 7th leading cause of cancer-related death in the world, while gemcitabine sensitivity is key important in PDAC therapy. SNHG14 is thought to be an oncogene in cancer progression. However, the possible role of SNHG14 underlying the progress of the PDAC cell, specifically in gemcitabine resistance remains to be determined. METHODS: We analyzed the PDAC-related data collected from TCGA. PDAC cell line (SW1990) was used as in vitro model. RT-qPCR and western blot were used to detect the autophagy-related gene expression level. MTT and flow cytometry approaches were used to determine cell viability and apoptosis rate. The luciferase reporter assay was used to confirm the direct interaction between SNHG14 and miR-101. The wound healing assay and transwell assay were used to detect the migration and invasion abilities of PDAC cells. RESULTS: The expression of SNHG14 was significantly higher in the PDAC tissues than in the normal tissues, while miR-101 was significantly downregulated in the PDAC tissues. Moreover, the correlation analysis showed that SNHG14 was negatively correlated with miR-101. The in vitro experiments furthermore confirmed their impacts on PDAC cells. Overexpression of SNHG14 and miR-101 inhibitor significantly enhanced cell proliferation, migration, and invasion rate of PDAC cell line. Moreover, SNHG14 knockdown and miR-101 mimics both led to attenuation of gemcitabine resistance-PDAC cell viability and promoted cell apoptosis rate, as well as the reduction of autophagy-related proteins (such as RAB5A and ATG4D). Overexpression of SNHG14 enhanced PDAC cell progression and inhibited cell apoptosis in gemcitabine treatment, as well as the increase of autophagy-related proteins, thus enhanced the chemoresistance of PDAC cells to gemcitabine. CONCLUSIONS: Collectively, we first time revealed that SNHG14 could sponge miR-101 to enhance PDAC cell progression and find the specific axis of SNHG14/miR-101/autophagy underlying the chemoresistance in PDAC cells to gemcitabine, which could promote the progress of PDAC therapy.
Authors: Kaihua Zhong; Dong Chen; Zhiming Wu; Xiaohong Wang; Bin Pan; Nanhui Chen; Weifeng Zhong Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2020-11-30