Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy

[Display omitted] Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenes...

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Veröffentlicht in:Biochemical pharmacology 2024-11, Vol.229, p.116460, Article 116460
Hauptverfasser: Tsai, Hsiao-Chi, Tsai, Ming-Hsui, Hua, Chun-Hung, Huang, Chun-Wei, Lu, Chien-Chi, Chen, Kwei-Jing, Yuan-Chien Chen, Michael, Lien, Ming-Yu, Tang, Chih-Hsin
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container_title Biochemical pharmacology
container_volume 229
creator Tsai, Hsiao-Chi
Tsai, Ming-Hsui
Hua, Chun-Hung
Huang, Chun-Wei
Lu, Chien-Chi
Chen, Kwei-Jing
Yuan-Chien Chen, Michael
Lien, Ming-Yu
Tang, Chih-Hsin
description [Display omitted] Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.
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Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.</description><identifier>ISSN: 0006-2952</identifier><identifier>ISSN: 1873-2968</identifier><identifier>EISSN: 1873-2968</identifier><identifier>DOI: 10.1016/j.bcp.2024.116460</identifier><identifier>PMID: 39098731</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing - antagonists &amp; inhibitors ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - therapeutic use ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - genetics ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; Cisplatin - pharmacology ; Cisplatin - therapeutic use ; Drug Resistance, Neoplasm ; Female ; Hsa_circ_0002722 ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mouth Neoplasms - drug therapy ; Mouth Neoplasms - genetics ; Mouth Neoplasms - metabolism ; Mouth Neoplasms - pathology ; OSCC ; Platinum resistance ; RNA, Circular - genetics ; RNA, Circular - metabolism ; Transcription Factors - antagonists &amp; inhibitors ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Verteporfin - pharmacology ; Verteporfin - therapeutic use ; Xenograft Model Antitumor Assays - methods ; YAP ; YAP-Signaling Proteins - metabolism</subject><ispartof>Biochemical pharmacology, 2024-11, Vol.229, p.116460, Article 116460</ispartof><rights>2024 Elsevier Inc.</rights><rights>Copyright © 2024 Elsevier Inc. 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Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. 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inhibitors</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Verteporfin - pharmacology</topic><topic>Verteporfin - therapeutic use</topic><topic>Xenograft Model Antitumor Assays - methods</topic><topic>YAP</topic><topic>YAP-Signaling Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsai, Hsiao-Chi</creatorcontrib><creatorcontrib>Tsai, Ming-Hsui</creatorcontrib><creatorcontrib>Hua, Chun-Hung</creatorcontrib><creatorcontrib>Huang, Chun-Wei</creatorcontrib><creatorcontrib>Lu, Chien-Chi</creatorcontrib><creatorcontrib>Chen, Kwei-Jing</creatorcontrib><creatorcontrib>Yuan-Chien Chen, Michael</creatorcontrib><creatorcontrib>Lien, Ming-Yu</creatorcontrib><creatorcontrib>Tang, Chih-Hsin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsai, Hsiao-Chi</au><au>Tsai, Ming-Hsui</au><au>Hua, Chun-Hung</au><au>Huang, Chun-Wei</au><au>Lu, Chien-Chi</au><au>Chen, Kwei-Jing</au><au>Yuan-Chien Chen, Michael</au><au>Lien, Ming-Yu</au><au>Tang, Chih-Hsin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy</atitle><jtitle>Biochemical pharmacology</jtitle><addtitle>Biochem Pharmacol</addtitle><date>2024-11</date><risdate>2024</risdate><volume>229</volume><spage>116460</spage><pages>116460-</pages><artnum>116460</artnum><issn>0006-2952</issn><issn>1873-2968</issn><eissn>1873-2968</eissn><abstract>[Display omitted] Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.</abstract><cop>England</cop><pub>Elsevier Inc</pub><pmid>39098731</pmid><doi>10.1016/j.bcp.2024.116460</doi><orcidid>https://orcid.org/0000-0002-7113-8352</orcidid></addata></record>
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subjects Adaptor Proteins, Signal Transducing - antagonists & inhibitors
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - genetics
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Line, Tumor
Cisplatin - pharmacology
Cisplatin - therapeutic use
Drug Resistance, Neoplasm
Female
Hsa_circ_0002722
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms - drug therapy
Mouth Neoplasms - genetics
Mouth Neoplasms - metabolism
Mouth Neoplasms - pathology
OSCC
Platinum resistance
RNA, Circular - genetics
RNA, Circular - metabolism
Transcription Factors - antagonists & inhibitors
Transcription Factors - genetics
Transcription Factors - metabolism
Verteporfin - pharmacology
Verteporfin - therapeutic use
Xenograft Model Antitumor Assays - methods
YAP
YAP-Signaling Proteins - metabolism
title Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy
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