LncRNA SNHG12 in extracellular vesicles derived from carcinoma-associated fibroblasts promotes cisplatin resistance in non-small cell lung cancer cells
| Autor: | Deli Tan, Gang Li, Peng Zhang, Chao Peng, Bo He |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Lung Neoplasms
cisplatin resistant rna-binding proteins Bioengineering General Medicine Applied Microbiology and Biotechnology respiratory tract diseases carcinoma-associated fibroblasts Cancer-Associated Fibroblasts lncrna snhg12 A549 Cells Drug Resistance Neoplasm Carcinoma Non-Small-Cell Lung Humans RNA Long Noncoding hur Cisplatin extracellular vesicles non-small cell lung cancer TP248.13-248.65 Research Article Research Paper rna stability Biotechnology |
| Zdroj: | Bioengineered, Vol 13, Iss 1, Pp 1838-1857 (2022) Bioengineered article-version (VoR) Version of Record |
| ISSN: | 2165-5987 2165-5979 |
| Popis: | Non-small-cell lung cancer (NSCLC) is defined as the most universally diagnosed class of lung cancer. Cisplatin (DDP) is an effective drug for NSCLC, but tumors are prone to drug resistance. The current study set out to evaluate the regulatory effect of long non-coding RNA (lncRNA) small nucleolar RNA host gene 12 (SNHG12) in extracellular vesicles (EVs) derived from carcinoma-associated fibroblasts (CAFs) on DDP resistance in NSCLC cells. Firstly, NSCLC cells were treated with EVs, followed by detection of cell activity, IC50 values, cell proliferation and apoptosis, and Cy3-SNHG12. We observed that CAFs-EVs promoted IC50 values and cell proliferation and inhibited apoptosis. In addition, we learned that lncRNA SNHG12 carried by CAFs-EVs into NSCLC facilitated DDP resistance of NSCLC cells. Furthermore, ELAV like RNA binding protein 1 (HuR/ELAVL1) binding to lncRNA SNHG12 and X-linked inhibitor of apoptosis (XIAP) was verified and RNA stability of XIAP was also verified CAFs-EVs promoted RNA stability and transcription of XIAP, while silencing HuR could partially-reverse this promoting effect. Further joint experimentation showed that silencing XIAP partially inhibited DDP resistance in NSCLC cells. Additionally, the tumor growth and the positive rate of Ki67 and HuR were detected, which showed that CAFs-oe-EVs promoted the tumor and the positive rate of Ki67, as well as the levels of lncRNA SNHG12, HuR, and XIAP in vivo. Collectively, our findings indicated that lncRNA SNHG12 carried by CAFs-EVs into NSCLC cells promoted RNA stability and XIAP transcription by binding to HuR, thus augmenting DDP resistance in NSCLC cells. |
| Databáze: | OpenAIRE |
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