Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors

Mu, Qingchun; Y, Lv; Luo, Chunmei; Liu, Xiaojing; Huang, Chun‐Ming; Xiu, Youcheng; Tang, Longguang

doi:10.3389/fphar.2021.709324

Cited by 28 publications

(15 citation statements)

References 158 publications

(190 reference statements)

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“…Patients with recurrent, progressive, and metastatic cervical cancer have an obviously poor overall prognosis once resistant to CP 36 . Research on circRNA in CP resistance has attracted increasing attention in recent years 37 . In this study, we found that circARHGAP5, a direct RNA target positively regulated by ΔNp63α, contributed to inducing platinum‐mediated apoptosis.…”

Section: Discussionmentioning

confidence: 65%

Circular RNA ARHGAP5 inhibits cisplatin resistance in cervical squamous cell carcinoma by interacting with AUF1

et al. 2023

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Cervical squamous cell carcinoma (CSCC) is one of the leading causes of cancer death in women worldwide. Patients with advanced cervical carcinoma always have a poor prognosis once resistant to cisplatin due to the lack of effective treatment. It is urgent to investigate the molecular mechanisms of cisplatin resistance. Circular RNAs (circRNAs) are known to exert their regulatory functions in a series of malignancies. However, their effects on CSCC remain to be elucidated. Here, we found that cytoplasmic circARHGAP5, derived from second and third exons of the ARHGAP5 gene, was downregulated in cisplatin‐resistant tissues compared with normal cervix tissues and untreated cervical cancer tissues. In addition, experiments from overexpression/knockdown cell lines revealed that circARHGAP5 could inhibit cisplatin‐mediated cell apoptosis in CSCC cells both in vitro and in vivo. Mechanistically, circARHGAP5 interacted with AU‐rich element RNA‐binding protein (AUF1) directly. Overexpression of AUF1 could also inhibit cell apoptosis mediated by cisplatin. Furthermore, we detected the potential targets of AUF1 related to the apoptotic pathway and found that bcl‐2‐like protein 11 (BIM) was not only negatively regulated by AUF1 but positively regulated by circARHGAP5, which indicated that BIM mRNA might be degraded by AUF1 and thereby inhibited tumor cell apoptosis. Collectively, our data indicated that circARHGAP5 directly bound to AUF1 and prevented AUF1 from interacting with BIM mRNA, thereby playing a pivotal role in cisplatin resistance in CSCC. Our study provides insights into overcoming cancer resistance to cisplatin treatment.

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Section: Discussionmentioning

confidence: 65%

Circular RNA ARHGAP5 inhibits cisplatin resistance in cervical squamous cell carcinoma by interacting with AUF1

et al. 2023

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“…Indeed, chloroquine, an autophagy inhibitor, was proven to mitigate the NSCLC cells’ resistance to erlotinib ( Zou et al, 2013 ) and was co-administrated with radiation therapy for treating brain metastases, acquiring superior outcomes compared with radiation therapy alone ( Rojas-Puentes et al, 2013 ). Hence, it is reasonable to hypothesize that targeting the circRNA–autophagy axis would greatly contribute to overcoming chemo- or radio-resistance of cancer cells ( Ishaq et al, 2020 ; Mu et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Circular RNA-regulated autophagy is involved in cancer progression

Zhou

Lin

Wang

et al. 2022

Front. Cell Dev. Biol.

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Circular RNAs (circRNAs) are a sort of long, non-coding RNA molecules with a covalently closed continuous ring structure without 5'-3' polarity and poly-A tail. The modulative role of circRNAs in malignant diseases has been elucidated by many studies in recent years via bioinformatics and high-throughput sequencing technologies. Generally, circRNA affects the proliferative, invasive, and migrative capacity of malignant cells via various mechanisms, exhibiting great potential as novel biomarkers in the diagnoses or treatments of malignancies. Meanwhile, autophagy preserves cellular homeostasis, serving as a vital molecular process in tumor progression. Mounting studies have demonstrated that autophagy can not only contribute to cancer cell survival but can also induce autophagic cell death in specific conditions. A growing number of research studies have indicated that there existed abundant associations between circRNAs and autophagy. Herein, we systemically reviewed and discussed recent studies on this topic in different malignancies and concluded that the circRNA–autophagy axis played crucial roles in the proliferation, metastasis, invasion, and drug or radiation resistance of different tumor cells.

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“…Cisplatin is a chemotherapeutic drug used for the treatment of a wide variety of cancers, including lung, bladder, ovarian, liver, and breast cancer [117,118]. Although cisplatin exerts considerable therapeutic effect, the resistance develops after long-term use and thus causes cancer recurrence and decreased overall survival.…”

Section: Cisplatinmentioning

confidence: 99%

“…Although cisplatin exerts considerable therapeutic effect, the resistance develops after long-term use and thus causes cancer recurrence and decreased overall survival. Demonstrating the effect of circRNAs on cisplatin resistance in recent years and understanding the underlying mechanisms will provide potential new strategies to improve the therapeutic efficiency in breast cancer treatment [117]. circUBAP2 was shown to enhance the expression of cisplatin-resistant TNBC, and the TNBC sensitivity against cisplatin may be increased by silencing the circUBAP2.…”

Section: Cisplatinmentioning

confidence: 99%

circRNAs in drug resistance of breast cancer

Mısır¹,

YAMAN²,

PETROVIĆ³

et al. 2022

Oncology Research

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Breast cancer (BC) is the most common heterogeneous disease in women and one of the leading causes of cancer-related death. Surgery, chemotherapy, radiotherapy, hormone, and targeted therapy are the gold standards for BC treatment. One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics, resistance that severely limits the use and effectiveness of the drugs used for BC treatment.Therefore, it is essential to develop new strategies to improve therapeutic efficacy. Circular RNAs (circRNAs) are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5′, and 3′; ends.Accumulating evidence suggests that circRNAs have a vital role in cancer development, progression, and BC resistance to chemotherapy. The purpose of this review is to discuss the biological properties of circRNAs, and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment, by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance, such as drug efflux, apoptosis dysfunction, autophagy, and DNA damage repair. CircRNAs are associated with drug resistance via ATP-binding cassette (ABC) efflux transporters, while some others by inhibition of cell apoptosis, thus leading to resistance to tamoxifen in BC cells. In contrast, others are involved in the promotion of BC cells chemoresistance by doxorubicininduced autophagy. CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment. CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.

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Research Progress on the Functions and Mechanism of circRNA in Cisplatin Resistance in Tumors

Cited by 28 publications

References 158 publications

Circular RNA ARHGAP5 inhibits cisplatin resistance in cervical squamous cell carcinoma by interacting with AUF1

Circular RNA ARHGAP5 inhibits cisplatin resistance in cervical squamous cell carcinoma by interacting with AUF1

Circular RNA-regulated autophagy is involved in cancer progression

circRNAs in drug resistance of breast cancer

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