miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways

Bi, Guoshu; Liang, Jiaqi; Zhao, Mengnan; Zhang, Huan; Jin, Xing; Lu, Tao; Zheng, Yuansheng; Bian, Yunyi; Chen, Zhencong; Huang, Yiwei; Besskaya, Valeria; Zhan, Cheng; Wang, Qun; Tan, Lijie

doi:10.1016/j.omtn.2022.03.020

Cited by 42 publications

(35 citation statements)

References 77 publications

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“…Cisplatin promotes tumor cell apoptosis by forming an adduct with the DNA of tumor cells, thereby achieving its anti-tumor effect [ 32 ]. Many studies have confirmed that the decrease in cell cycle arrest is the key factor in tumor cisplatin resistance [ 33 , 34 , 35 ]. We found that the overexpression of miR - 660 decreased the cell proliferation capacity and increased the cell apoptosis rate and cell cycle arrest in cisplatin-treated A549/CDDP and CALU-3 cells.…”

Section: Discussionmentioning

confidence: 99%

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Wang

Zhou

Chen

et al. 2023

Genes

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Increasing evidence suggests that microRNAs’ (miRNAs) abnormal expression is one of the main factors of chemotherapy resistance in various cancers. However, the role of miRNAs in lung adenocarcinoma (LUAD) resistance to cisplatin is still unclear. In this study, we analyzed a microarray dataset to investigate miRNAs related to cisplatin resistance in LUAD. The expression of miRNAs in LUAD tissues and cell lines was detected using real-time quantitative polymerase chain reaction (RT-qPCR). Special AT-Rich Sequence-Binding Protein 2 (SATB2) in LUAD cell lines was detected using RT-qPCR and Western blot. Cell proliferation was measured by CCK8 and colony formation assays, while cell cycle and apoptosis were measured by flow cytometry. A dual-luciferase reporter assay was performed to confirm that SATB2 is a target gene of microRNA-660 (miR-660). We showed that the expression of miR-660 was not only decreased in LUAD cells and tissues but also further decreased in the cisplatin-resistant A549 cell line. The overexpression of miR-660 increased cisplatin sensitivity in LUAD cells. In addition, we identified SATB2 as a direct target gene of miR-660. We also revealed that miR-660 increased cisplatin sensitivity in LUAD cells via targeting SATB2. In conclusion, miR-660/SATB2 axis is a key regulator of cisplatin resistance in LUAD.

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Section: Discussionmentioning

confidence: 99%

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Wang

Zhou

Chen

et al. 2023

Genes

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“…More and more studies have shown that non-coding RNAs play an important regulatory role in tumor development [ 145 , 146 ]. In recent years, as researchers have deepened their research on ferroptosis, more and more non-coding RNAs have been proven to regulate ferroptosis in tumor cells [ 96 , 147 , 148 ].…”

Section: Targets Of Ferroptosis In Lung Cancermentioning

confidence: 99%

“…Exosomal miR-4443 can reduce the expression level of methyltransferase-like 3 (METTL3) by targeting METTL3, and increase the level of FSP1 by N6-methyladenosine (m6A) methylation to inhibit ferroptosis and make NSCLC cells resistant to CDDP [ 151 ]. At the same time, miR-6077 could protect LUAD cells from cell death induced by CDDP combined with pemetrexed (PEM) by regulating the KEAP1-Nrf2-SLC7A11/NQO1 axis to mediate ferroptosis [ 147 ]. When miR-27a-3p is overexpressed, it directly binds to the 3’-UTR of SLC7A11, leading to its inhibition and subsequently reducing the ferroptosis induced by erastin.…”

Section: Targets Of Ferroptosis In Lung Cancermentioning

confidence: 99%

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Xing

Guo

et al. 2023

Cell Death Discov.

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Lung cancer is a common malignant tumor that occurs in the human body and poses a serious threat to human health and quality of life. The existing treatment methods mainly include surgical treatment, chemotherapy, and radiotherapy. However, due to the strong metastatic characteristics of lung cancer and the emergence of related drug resistance and radiation resistance, the overall survival rate of lung cancer patients is not ideal. There is an urgent need to develop new treatment strategies or new effective drugs to treat lung cancer. Ferroptosis, a novel type of programmed cell death, is different from the traditional cell death pathways such as apoptosis, necrosis, pyroptosis and so on. It is caused by the increase of iron-dependent reactive oxygen species due to intracellular iron overload, which leads to the accumulation of lipid peroxides, thus inducing cell membrane oxidative damage, affecting the normal life process of cells, and finally promoting the process of ferroptosis. The regulation of ferroptosis is closely related to the normal physiological process of cells, and it involves iron metabolism, lipid metabolism, and the balance between oxygen-free radical reaction and lipid peroxidation. A large number of studies have confirmed that ferroptosis is a result of the combined action of the cellular oxidation/antioxidant system and cell membrane damage/repair, which has great potential application in tumor therapy. Therefore, this review aims to explore potential therapeutic targets for ferroptosis in lung cancer by clarifying the regulatory pathway of ferroptosis. Based on the study of ferroptosis, the regulation mechanism of ferroptosis in lung cancer was understood and the existing chemical drugs and natural compounds targeting ferroptosis in lung cancer were summarized, with the aim of providing new ideas for the treatment of lung cancer. In addition, it also provides the basis for the discovery and clinical application of chemical drugs and natural compounds targeting ferroptosis to effectively treat lung cancer.

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“…It decreased ferroportin-overloaded intracellular iron and, finally, resulted in lipid peroxidation and ferroptosis ( Wei et al, 2021 ). Bi, G. et al reported that the miR-6077-Keap1-Nrf2-SLC7A11/NQO1 axis impedes ferroptosis and induces cisplatin (CDDP)/pemetrexed (PEM) resistance ( Bi et al, 2022 ).…”

Section: Regulation Of Ncrnas Related With Ferroptosis In Cancersmentioning

confidence: 99%

Regulation of ncRNAs involved with ferroptosis in various cancers

Zeng

Zhu

et al. 2023

Front. Genet.

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As a special pattern of programmed cell death, ferroptosis is reported to participate in several processes of tumor progression, including regulating proliferation, suppressing apoptotic pathways, increasing metastasis, and acquiring drug resistance. The marked features of ferroptosis are an abnormal intracellular iron metabolism and lipid peroxidation that are pluralistically modulated by ferroptosis-related molecules and signals, such as iron metabolism, lipid peroxidation, system Xc−, GPX4, ROS production, and Nrf2 signals. Non-coding RNAs (ncRNAs) are a type of functional RNA molecules that are not translated into a protein. Increasing studies demonstrate that ncRNAs have a diversity of regulatory roles in ferroptosis, thus influencing the progression of cancers. In this study, we review the fundamental mechanisms and regulation network of ncRNAs on ferroptosis in various tumors, aiming to provide a systematic understanding of recently emerging non-coding RNAs and ferroptosis.

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miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways

Cited by 42 publications

References 77 publications

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

microRNA-660 Enhances Cisplatin Sensitivity via Decreasing SATB2 Expression in Lung Adenocarcinoma

Ferroptosis in lung cancer: a novel pathway regulating cell death and a promising target for drug therapy

Regulation of ncRNAs involved with ferroptosis in various cancers

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