LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944
Gemcitabine (GEM) is the gold-standard therapeutic regimen for patients with pancreatic cancer (PC); however, patients may receive limited benefits due to the drug resistance of GEM. LncRNA SNHG6 is reported to play key roles in drug resistance, but its role and molecular mechanism in PC remain inco...
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MDPI AG
2023-01-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/2/184 |
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| author | Ge Gao Xin Li Hui Wu Ling-li Huang Yu-xin Lin Zhi Huo Zhong-yuan Xiang Xiao Zhou |
| author_facet | Ge Gao Xin Li Hui Wu Ling-li Huang Yu-xin Lin Zhi Huo Zhong-yuan Xiang Xiao Zhou |
| author_sort | Ge Gao |
| collection | DOAJ |
| description | Gemcitabine (GEM) is the gold-standard therapeutic regimen for patients with pancreatic cancer (PC); however, patients may receive limited benefits due to the drug resistance of GEM. LncRNA SNHG6 is reported to play key roles in drug resistance, but its role and molecular mechanism in PC remain incompletely understood. We found that LncRNA SNHG6 is drastically downregulated in GEM-resistant PC and is positively correlated with the survival of PC patients. With the help of bioinformatic analysis and molecular approaches, we show that LncRNA SNHG6 can sponge miR-944, therefore causing the upregulation of the target gene KPNA5. In vitro experiments showed that LncRNA SNHG6 and KPNA5 suppress PC cell proliferation and colony formation. The Upregulation of LncRNA SNHG6 and KPNA5 increases the response of GEM-resistant PANC-1 cells to GEM. We also show that the expression of KPNA5 is higher in patients without GEM resistance than in those who developed GEM resistance. In summary, our findings indicate that the LncRNA SNHG6/miR944/KPNA5 axis plays a pivotal role in overcoming GEM resistance, and targeting this axis may contribute to an increasing of the benefits of PC patients from GEM treatment. |
| first_indexed | 2024-03-11T08:18:24Z |
| format | Article |
| id | doaj.art-e1abc03893394fdb92fd55b2769ec4fc |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T08:18:24Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj.art-e1abc03893394fdb92fd55b2769ec4fc2023-11-16T22:36:10ZengMDPI AGPharmaceuticals1424-82472023-01-0116218410.3390/ph16020184LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944Ge Gao0Xin Li1Hui Wu2Ling-li Huang3Yu-xin Lin4Zhi Huo5Zhong-yuan Xiang6Xiao Zhou7Department of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaDepartment of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaSchool of Basic Medical Sciences, Central South University, Changsha 410013, ChinaDepartment of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, ChinaDepartment of Clinical Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha 410013, ChinaGemcitabine (GEM) is the gold-standard therapeutic regimen for patients with pancreatic cancer (PC); however, patients may receive limited benefits due to the drug resistance of GEM. LncRNA SNHG6 is reported to play key roles in drug resistance, but its role and molecular mechanism in PC remain incompletely understood. We found that LncRNA SNHG6 is drastically downregulated in GEM-resistant PC and is positively correlated with the survival of PC patients. With the help of bioinformatic analysis and molecular approaches, we show that LncRNA SNHG6 can sponge miR-944, therefore causing the upregulation of the target gene KPNA5. In vitro experiments showed that LncRNA SNHG6 and KPNA5 suppress PC cell proliferation and colony formation. The Upregulation of LncRNA SNHG6 and KPNA5 increases the response of GEM-resistant PANC-1 cells to GEM. We also show that the expression of KPNA5 is higher in patients without GEM resistance than in those who developed GEM resistance. In summary, our findings indicate that the LncRNA SNHG6/miR944/KPNA5 axis plays a pivotal role in overcoming GEM resistance, and targeting this axis may contribute to an increasing of the benefits of PC patients from GEM treatment.https://www.mdpi.com/1424-8247/16/2/184LncRNA SNHG6Gemcitabine resistanceKPNA5miR-944pancreatic cancer |
| spellingShingle | Ge Gao Xin Li Hui Wu Ling-li Huang Yu-xin Lin Zhi Huo Zhong-yuan Xiang Xiao Zhou LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 Pharmaceuticals LncRNA SNHG6 Gemcitabine resistance KPNA5 miR-944 pancreatic cancer |
| title | LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 |
| title_full | LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 |
| title_fullStr | LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 |
| title_full_unstemmed | LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 |
| title_short | LncRNA SNHG6 Upregulates KPNA5 to Overcome Gemcitabine Resistance in Pancreatic Cancer via Sponging miR-944 |
| title_sort | lncrna snhg6 upregulates kpna5 to overcome gemcitabine resistance in pancreatic cancer via sponging mir 944 |
| topic | LncRNA SNHG6 Gemcitabine resistance KPNA5 miR-944 pancreatic cancer |
| url | https://www.mdpi.com/1424-8247/16/2/184 |
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