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Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy

BACKGROUND: Gastric carcinoma (GC) is one of the most deadly diseases due to tumour metastasis and resistance to therapy. Understanding the molecular mechanism of tumour progression and drug resistance will improve therapeutic efficacy and develop novel intervention strategies. METHODS: Differential...

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Autores principales: Xiao, Yu‐Feng, Li, Bo‐Sheng, Liu, Jing‐Jing, Wang, Su‐Min, Liu, Jiao, Yang, Huan, Hu, Yi‐Yang, Gong, Chun‐Li, Li, Ji‐Liang, Yang, Shi‐Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043116/
https://www.ncbi.nlm.nih.gov/pubmed/35474446
http://dx.doi.org/10.1002/ctm2.691
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author Xiao, Yu‐Feng
Li, Bo‐Sheng
Liu, Jing‐Jing
Wang, Su‐Min
Liu, Jiao
Yang, Huan
Hu, Yi‐Yang
Gong, Chun‐Li
Li, Ji‐Liang
Yang, Shi‐Ming
author_facet Xiao, Yu‐Feng
Li, Bo‐Sheng
Liu, Jing‐Jing
Wang, Su‐Min
Liu, Jiao
Yang, Huan
Hu, Yi‐Yang
Gong, Chun‐Li
Li, Ji‐Liang
Yang, Shi‐Ming
author_sort Xiao, Yu‐Feng
collection PubMed
description BACKGROUND: Gastric carcinoma (GC) is one of the most deadly diseases due to tumour metastasis and resistance to therapy. Understanding the molecular mechanism of tumour progression and drug resistance will improve therapeutic efficacy and develop novel intervention strategies. METHODS: Differentially expressed long non‐coding RNAs (lncRNAs) in clinical specimens were identified by LncRNA microarrays and validated in different clinical cohorts by quantitative real‐time polymerase chain reaction (qRT‐PCR), in situ hybridisation and bioinformatics analysis. Biological functions of lncRNA were investigated by using cell proliferation assays, migration assays, xenograft tumour models and bioinformatics analysis. Effects of lncSLCO1C1 on GC cell survival were assessed by comet assays and immunofluorescence assays. Underlying molecular mechanisms were further explored by using a number of technologies including RNA pull‐down, mass spectrometry analysis, RNA immunoprecipitation, co‐immunoprecipitation, miRNA sequencing, luciferase reporter assays and molecular modelling. RESULTS: LncSLCO1C1 was highly upregulated in GC tissue samples and associated with GC patients’ poor overall survival. Overexpression of lncSLCO1C1 promoted proliferation and migration, whereas decreased lncSLCO1C1 expression produced the opposite effects. lncSLCO1C1 also mediated tumour resistance to chemotherapy with oxaliplatin by reducing DNA damage and increasing cell proliferation. Despite sequence overlapping between lncSLCO1C1 and PDE3A, alternations of PDE3A expression had no effect on the GC cell progression, indicating that lncSLCO1C1, not PDE3A, related with the progression of GC cells. Mechanistically, lncSLCO1C1 serves as a scaffold for the structure‐specific recognition protein 1 (SSRP1)/H2A/H2B complex and regulates the function of SSRP1 in reducing DNA damage. Meanwhile, lncSLCO1C1 functions as a sponge to adsorb miR‐204‐5p and miR‐211‐5p that target SSRP1 mRNA, and thus increases SSRP1 expression. Patients with high expressions of both lncSLCO1C1 and SSRP1 have poor overall survival, highlighting the role of lncSLCO1C1 in GC progression. CONCLUSIONS: LncSLCO1C1 promotes GC progression by enhancing cell growth and preventing DNA damage via interacting and scaffolding the SSRP1/H2A/H2b complex and absorbing both miR‐211‐5p and miR‐204‐5p to increase SSRP1 expression.
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spelling pubmed-90431162022-04-28 Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy Xiao, Yu‐Feng Li, Bo‐Sheng Liu, Jing‐Jing Wang, Su‐Min Liu, Jiao Yang, Huan Hu, Yi‐Yang Gong, Chun‐Li Li, Ji‐Liang Yang, Shi‐Ming Clin Transl Med Research Articles BACKGROUND: Gastric carcinoma (GC) is one of the most deadly diseases due to tumour metastasis and resistance to therapy. Understanding the molecular mechanism of tumour progression and drug resistance will improve therapeutic efficacy and develop novel intervention strategies. METHODS: Differentially expressed long non‐coding RNAs (lncRNAs) in clinical specimens were identified by LncRNA microarrays and validated in different clinical cohorts by quantitative real‐time polymerase chain reaction (qRT‐PCR), in situ hybridisation and bioinformatics analysis. Biological functions of lncRNA were investigated by using cell proliferation assays, migration assays, xenograft tumour models and bioinformatics analysis. Effects of lncSLCO1C1 on GC cell survival were assessed by comet assays and immunofluorescence assays. Underlying molecular mechanisms were further explored by using a number of technologies including RNA pull‐down, mass spectrometry analysis, RNA immunoprecipitation, co‐immunoprecipitation, miRNA sequencing, luciferase reporter assays and molecular modelling. RESULTS: LncSLCO1C1 was highly upregulated in GC tissue samples and associated with GC patients’ poor overall survival. Overexpression of lncSLCO1C1 promoted proliferation and migration, whereas decreased lncSLCO1C1 expression produced the opposite effects. lncSLCO1C1 also mediated tumour resistance to chemotherapy with oxaliplatin by reducing DNA damage and increasing cell proliferation. Despite sequence overlapping between lncSLCO1C1 and PDE3A, alternations of PDE3A expression had no effect on the GC cell progression, indicating that lncSLCO1C1, not PDE3A, related with the progression of GC cells. Mechanistically, lncSLCO1C1 serves as a scaffold for the structure‐specific recognition protein 1 (SSRP1)/H2A/H2B complex and regulates the function of SSRP1 in reducing DNA damage. Meanwhile, lncSLCO1C1 functions as a sponge to adsorb miR‐204‐5p and miR‐211‐5p that target SSRP1 mRNA, and thus increases SSRP1 expression. Patients with high expressions of both lncSLCO1C1 and SSRP1 have poor overall survival, highlighting the role of lncSLCO1C1 in GC progression. CONCLUSIONS: LncSLCO1C1 promotes GC progression by enhancing cell growth and preventing DNA damage via interacting and scaffolding the SSRP1/H2A/H2b complex and absorbing both miR‐211‐5p and miR‐204‐5p to increase SSRP1 expression. John Wiley and Sons Inc. 2022-04-26 /pmc/articles/PMC9043116/ /pubmed/35474446 http://dx.doi.org/10.1002/ctm2.691 Text en © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Xiao, Yu‐Feng
Li, Bo‐Sheng
Liu, Jing‐Jing
Wang, Su‐Min
Liu, Jiao
Yang, Huan
Hu, Yi‐Yang
Gong, Chun‐Li
Li, Ji‐Liang
Yang, Shi‐Ming
Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title_full Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title_fullStr Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title_full_unstemmed Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title_short Role of lncSLCO1C1 in gastric cancer progression and resistance to oxaliplatin therapy
title_sort role of lncslco1c1 in gastric cancer progression and resistance to oxaliplatin therapy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043116/
https://www.ncbi.nlm.nih.gov/pubmed/35474446
http://dx.doi.org/10.1002/ctm2.691
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