Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis

Jin, Wenhua; Zhang, Hua; Li, Meng; Shi, Lin

doi:10.1089/cbr.2019.3525

Cited by 8 publications

(5 citation statements)

References 28 publications

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“… 34 , 35 LncRNA ROR could regulate cell growth, metastasis and DDP resistance in GC via the miR-519d-3p/HMGA2 axis. 36 Overexpression of lncRNA SNHG5 could upregulate Bax, MDR1 and MRP1, downregulate Bcl-2 and increase the Bcl-2/Bax ratio in GC cells, thereby resulting in DDP resistance in GC. 37 LncRNA UCA1 promotes DDP resistance in GC by recruiting EZH2 and activating the PI3K/AKT pathway; the UCA1-miR-27b pathway has also been implicated in the regulation of chemoresistance of GC cells.…”

Section: Resultsmentioning

confidence: 99%

Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

Li¹,

Lü²,

Zhou³

et al. 2021

OTT

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Purpose: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) play a vital role in the chemoresistance of gastric cancer (GC). The present systematic review summarises the emerging role, potential targets or pathways and regulatory mechanisms of lncRNAs involved in chemoresistance and proposes a number of clinical implications of lncRNAs as novel therapeutic targets for GC. Methods: Studies on lncRNAs involved in the chemoresistance of GC published until July 2020 in the PubMed and Web of Science databases were systematically reviewed and the expression form, role in chemoresistance, targets or pathways, corresponding drugs and potential mechanisms of relevant lncRNAs were summarised in detail. Results: A total of 48 studies were included in this systematic review. Amongst these studies, 32 involved single drug resistance and 16 involved in multidrug resistance (MDR). The 48 studies collected described 38 lncRNAs in the drug-resistant cells of GC, including 33 upregulated and 5 downregulated lncRNAs. Cisplatin (DDP) was the most studied drug and lncRNA MALAT1 was the most studied lncRNA related to the chemoresistance of GC. The potential mechanisms of chemoresistance for lncRNAs in GC mainly included, amongst others, reduction of apoptosis, induction of autophagy, repair of DNA damage, promotion of epithelial-mesenchymal transition (EMT) and regulation of the related signalling pathways. Conclusion:LncRNAs play a vital role in the chemoresistance of GC and are novel therapeutic targets for the disease. Detailed chemoresistance mechanisms, translational studies and clinical trials on lncRNAs in GC are urgently needed.

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Section: Resultsmentioning

confidence: 99%

Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

Li¹,

Lü²,

Zhou³

et al. 2021

OTT

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“…Previous studies showed that miR‐519d‐3p inhibited high mobility group protein family members and antagonized cisplatin resistance of gastric cancer and nonsmall cell lung cancer 32–34 . One miRNA is expected to target many mRNAs which may take part in cancer progression, including chemoresistance.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐519d‐3p antagonizes osteosarcoma resistance against cisplatin by targeting PD‐L1

Wang

Zhenjun

Qiu

et al. 2021

Molecular Carcinogenesis

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Accumulating evidence indicates that a ligand of programmed cell death receptor‐1 (PD‐L1) participates in the progression and recurrence of multiple malignancies, including osteosarcoma. Nevertheless, the role of PD‐L1 in chemoresistance development is not fully understood. In the current study, we aim to clarify the interaction of miR‐519d‐3p and PD‐L1 in the development of cisplatin resistance. Immunohistochemistry, quantitative reverse‐transcription polymerase reaction, and Western blot were used to evaluate PD‐L1 expression. MTT and transwell migration assays were used to measure cell growth and motility, respectively. ENCORI, miRCode, and miRDB databases were recruited to predict candidate miRNAs targeting PD‐L1. The binding sequences of miR‐519d‐3p and PD‐L1 3ʹ untranslated region were identified by dual‐luciferase reporter and RNA immunoprecipitation assays. Flow cytometric analysis was conducted to measure the cycle distribution and cell apoptosis. Metastatic mouse models were generated with cisplatin‐resistant sublines by intravenous injection. We found that PD‐L1 expression was positively correlated to cisplatin resistance and metastasis, whereas miR‐519d‐3p expression was reduced in cisplatin‐resistant specimens and was negatively correlated to cisplatin resistance and metastasis of osteosarcoma. We demonstrated that miR‐519d‐3p overexpression reversed cisplatin resistance, induced G1/S phase arrest and apoptosis. In addition, we proved that miR‐519d‐3p inhibited lung metastasis by establishing cisplatin‐resistant MG63 metastatic xenograft models. The present findings suggest that miR‐519d‐3p/PD‐L1 axis is a novel signaling pathway contributing to cisplatin resistance. Our study provides new clues for curing refractory osteosarcoma beyond immune checkpoint inhibitors.

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“…Other molecular pathways and mechanisms have been explored on the influence that exerts linc-ROR in EMT and metastasis. Jin et al [ 111 ] demonstrated that linc-ROR knockdown downregulated the high mobility group AT-hook 2 (HMGA2) gene and upregulated miR-519d-3p to restrain migration, invasion, and EMT in gastric cancer, establishing a correlation with the miR-519d-3p/HMGA2 network. Similarly, the EMT phenotype induced by TGF-β1 was reversed after linc-ROR was knocked out in gallbladder cancer cells, whilst linc-ROR expression level was significantly associated with tumor sizes and lymph node metastasis [ 191 ].…”

Section: Linc-ror In Emt Cancer Invasion and Metastasismentioning

confidence: 99%

“…Cisplatin resistance has been associated with linc-ROR upregulation in cancer cells. In gastric cancer cell lines MKN45 and HGC-27, linc-ROR acted in the miR-519-d-3p/HMGA2 network to promote cisplatin resistance [ 111 ], whilst the same resistance was demonstrated in osteosarcoma samples via miR-153-3p/ABCB1 axis [ 170 ]. Surprisingly, linc-ROR expression increased the sensitivity of lung adenocarcinoma cells to cisplatin by targeting the PI3K/Akt/mTOR signaling pathway [ 88 ].…”

Section: Linc-ror In Drug Resistancementioning

confidence: 99%

Functional Relevance of the Long Intergenic Non-Coding RNA Regulator of Reprogramming (Linc-ROR) in Cancer Proliferation, Metastasis, and Drug Resistance

Peña-Flores

Enríquez-Espinoza

Muela-Campos

et al. 2023

ncRNA

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Cancer is responsible for more than 10 million deaths every year. Metastasis and drug resistance lead to a poor survival rate and are a major therapeutic challenge. Substantial evidence demonstrates that an increasing number of long non-coding RNAs are dysregulated in cancer, including the long intergenic non-coding RNA, regulator of reprogramming (linc-ROR), which mostly exerts its role as an onco-lncRNA acting as a competing endogenous RNA that sequesters micro RNAs. Although the properties of linc-ROR in relation to some cancers have been reviewed in the past, active research appends evidence constantly to a better comprehension of the role of linc-ROR in different stages of cancer. Moreover, the molecular details and some recent papers have been omitted or partially reported, thus the importance of this review aimed to contribute to the up-to-date understanding of linc-ROR and its implication in cancer tumorigenesis, progression, metastasis, and chemoresistance. As the involvement of linc-ROR in cancer is elucidated, an improvement in diagnostic and prognostic tools could promote and advance in targeted and specific therapies in precision oncology.

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Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis

Cited by 8 publications

References 28 publications

Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

Role of Long Non-Coding RNAs in the Chemoresistance of Gastric Cancer: A Systematic Review

MicroRNA‐519d‐3p antagonizes osteosarcoma resistance against cisplatin by targeting PD‐L1

Functional Relevance of the Long Intergenic Non-Coding RNA Regulator of Reprogramming (Linc-ROR) in Cancer Proliferation, Metastasis, and Drug Resistance

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