Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

Long, Gongwei; Ma, Siquan; Shi, Runlin; Sun, Yi; Hu, Zhiquan; Chen, Ke

doi:10.3390/cancers14040866

Cited by 10 publications

(8 citation statements)

References 195 publications

(221 reference statements)

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“…Accordingly, the development of not only novel anti-cancer agents but also strategies for chemosensitization of existing drugs should provide considerable improvement in oncologic outcomes of urothelial cancer. The molecular mechanisms underlying CDDP resistance are still far from being fully understood [13][14][15][16][17][18]. Meanwhile, androgen-mediated androgen receptor (AR) signaling has been implicated in the promotion of urothelial tumorigenesis, which may be a reason for a substantially higher risk of bladder cancer development in men than in women, as well as urothelial tumor progression [19].…”

Section: Ar Activity and Gabbr2 Expressionmentioning

confidence: 99%

“…The molecular mechanisms underlying CDDP resistance are still far from being fully understood [ 13 , 14 , 15 , 16 , 17 , 18 ]. Meanwhile, androgen-mediated androgen receptor (AR) signaling has been implicated in the promotion of urothelial tumorigenesis, which may be a reason for a substantially higher risk of bladder cancer development in men than in women, as well as urothelial tumor progression [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer

Elahi Najafi,

Yasui,

Teramoto

et al. 2023

IJMS

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The precise molecular mechanisms responsible for resistance to cisplatin-based chemotherapy in patients with bladder cancer remain elusive, while we have indicated that androgen receptor (AR) activity in urothelial cancer is associated with its sensitivity. Our DNA microarray analysis in control vs. AR-knockdown bladder cancer sublines suggested that the expression of a GABA B receptor GABBR2 and AR was correlated. The present study aimed to determine the functional role of GABBR2 in modulating cisplatin sensitivity in bladder cancer. AR knockdown and dihydrotestosterone treatment considerably reduced and induced, respectively, GABBR2 expression, and the effect of dihydrotestosterone was at least partially restored by an antiandrogen hydroxyflutamide. A chromatin immunoprecipitation assay further revealed the binding of AR to the promoter region of GABBR2 in bladder cancer cells. Meanwhile, GABBR2 expression was significantly elevated in a cisplatin-resistant bladder cancer subline, compared with control cells. In AR-positive bladder cancer cells, knockdown of GABBR2 or treatment with a selective GABA B receptor antagonist, CGP46381, considerably enhanced the cytotoxic activity of cisplatin. However, no additional effect of CGP46381 on cisplatin-induced growth suppression was seen in GABBR2-knockdown cells. Moreover, in the absence of cisplatin, CGP46381 treatment and GABBR2 knockdown showed no significant changes in cell proliferation or migration. These findings suggest that GABBR2 represents a key downstream effector of AR signaling in inducing resistance to cisplatin treatment. Accordingly, inhibition of GABBR2 has the potential of being a means of chemosensitization, especially in patients with AR/GABBR2-positive bladder cancer.

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Section: Ar Activity and Gabbr2 Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer

Elahi Najafi,

Yasui,

Teramoto

et al. 2023

IJMS

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“…lncRNAs are a class of single-stranded RNA molecules with more than 200 nucleotides that are important in molecular networks ( Guo et al, 2022 ). CircRNAs are a class of non-coding RNAs with high stability and significant clinical relevance ( Long et al, 2022 ). Intriguingly, as essential components, ncRNAs are selectively enriched in EVs, and ncRNAs loaded into EVs exert biological functions that modulate specific aspects of the onset and progression of ischemic stroke.…”

Section: The Role Of Extracellular Vesicles-derived From Neurons/neur...mentioning

confidence: 99%

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

Kang

Xin

et al. 2022

Front. Pharmacol.

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Neurons and neurogliocytes (oligodendrocytes, astrocytes, and microglia) are essential for maintaining homeostasis of the microenvironment in the central nervous system (CNS). These cells have been shown to support cell-cell communication via multiple mechanisms, most recently by the release of extracellular vesicles (EVs). Since EVs carry a variety of cargoes of nucleic acids, lipids, and proteins and mediate intercellular communication, they have been the hotspot of diagnosis and treatment. The mechanisms underlying CNS disorders include angiogenesis, autophagy, apoptosis, cell death, and inflammation, and cell-EVs have been revealed to be involved in these pathological processes. Ischemic stroke is one of the most common causes of death and disability worldwide. It results in serious neurological and physical dysfunction and even leads to heavy economic and social burdens. Although a large number of researchers have reported that EVs derived from these cells play a vital role in regulating multiple pathological mechanisms in ischemic stroke, the specific interactional relationships and mechanisms between specific cell-EVs and stroke treatment have not been clearly described. This review aims to summarize the therapeutic effects and mechanisms of action of specific cell-EVs on ischemia. Additionally, this study emphasizes that these EVs are involved in stroke treatment by inhibiting and activating various signaling pathways such as ncRNAs, TGF-β1, and NF-κB.

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“… 5 EIciRNAs are mainly located in the nucleus and may promote transcription of parent genes by connecting with U1 small nuclear ribonucleoprotein (snRNP) and RNA polymerase II (Pol II) at parental gene promoters 12 (Figure 1B ). However, the vast majority of circRNAs are transported into the cytoplasm and regulate mRNA expression by acting as sponges of microRNAs (miRNAs), which playing an important role in competitive endogenous RNA (ceRNA) networks 13 (Figure 1C ). ciRS‐7, also widely known as CDR1as, is present in human brain and mainly acts as sponge for miR‐7 with more than 70 miRNA target sites.…”

Section: The Structure and Function Of Circrnasmentioning

confidence: 99%

The roles and mechanisms of circular RNAs related to mTOR in cancers

Cao

Wang

et al. 2022

Clinical Laboratory Analysis

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Background Circular RNAs (circRNAs) are stable molecules with covalently closed structures that have an irreplaceable role in the occurrence, progression, and even treatment of plenty of cancers. Mammalian/mechanistic target of rapamycin (mTOR) is a key regulator in cancers and plays several biological functions, such as proliferation, migration, invasion, autophagy, and apoptosis. Methods All data were collected through PubMed and CNKI, using terms including “circRNA,” “mTOR,” “caner,” “signaling pathway,” “biomarker,” “diagnosis,” “treatment.” Articles published in Chinese and English were included. Results In this review, the expression, function, and mechanism of circRNA‐associated mTOR in cancers were described. CircRNA‐associated‐mTOR can regulate the progression and therapy of a variety of cancers in multiple signaling pathways, such as phosphatidylinositol‐3‐kinase (PI3K)/protein kinase B (Akt)/mTOR, mitogen‐activated protein kinase (MAPK)/mTOR, and AMP‐activated protein kinase (AMPK)/mTOR axis. These cancers including esophageal carcinoma (circLPAR3, ciRS‐7), gastric cancer (circNRIP1, hsa_circ_0010882, hsa_circ_0000117, hsa_circ_0072309, and circST3GAL6), colorectal cancer (hsa_circ_0000392, hsa_circ_0084927, hsa_circ_0104631, and circFBXW7), liver cancer (circC16orf62, hsa_circ_100338, hsa_circ_0004001, hsa_circ_0004123, hsa_circ_0075792, hsa_circ_0079299, and hsa_circ_0002130), pancreatic cancer (circ‐IARS and circRHOBTB3), renal carcinoma (ciRS‐7), bladder cancer (circUBE2K), prostate cancer (circMBOAT2 and circ‐ITCH), ovarian cancer (circEEF2, circRAB11FIP1, circMYLK, and circTPCN), endometrial cancer (hsa_circ_0002577 and circWHSC1), lung cancer (circHIPK3, hsa_circ_0001666), thyroid cancer (hsa_circ_0007694 and hsa_circ_0008274), glioma (circGFRA1, circ‐MAPK4, circPCMTD1, and hsa_circ_0037251), osteosarcoma (circTCF25), leukemia (circ‐PRKDC), and breast cancer (hsa_circ_0000199, circUBAP2, and circWHSC1).

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Circular RNAs and Drug Resistance in Genitourinary Cancers: A Literature Review

Cited by 10 publications

References 195 publications

GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer

GABBR2 as a Downstream Effector of the Androgen Receptor Induces Cisplatin Resistance in Bladder Cancer

The Emerging Role of Extracellular Vesicle Derived From Neurons/Neurogliocytes in Central Nervous System Diseases: Novel Insights Into Ischemic Stroke

The roles and mechanisms of circular RNAs related to mTOR in cancers

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