Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1

Zhu, Kun Yan; Ma, Xiaolong; Zhang, Chunlin

doi:10.7150/ijbs.24360

Cited by 227 publications

(248 citation statements)

References 50 publications

(46 reference statements)

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“…For circ‐PVT1, it has been found dysregulated in some cancer cells, and a few studies emerge to display the role of circ‐PVT1 as an oncogene in various cancers . For example, circ‐PVT1 expression is elevated in gastric cancer cells compared to normal gastric epithelium cells, and is also increased in CRC cell lines compared to normal human colon epithelial cell line .…”

Section: Discussionmentioning

confidence: 99%

“…Circular RNA PVT1 (Circ‐PVT1) has been reported to promote cell proliferation, migration and invasion but suppress cell apoptosis in several cancers, such as nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC) and head/neck squamous cell carcinoma, indicating that circ‐PVT1 might function as an oncogene in these cancers . In clinical practices, the abnormally overexpressed circ‐PVT1 has shown the potential to be a predictive factor for poor prognosis in patients with different malignancies as well . Considering different cancers present with the common feature of malignant proliferation, we hypothesized that the functions of circ‐PVT1 on promoting cancer cell proliferation and suppressing apoptosis might also be existed in EOC cells.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12][13] In clinical practices, the abnormally overexpressed circ-PVT1 has shown the potential to be a predictive factor for poor prognosis in patients with different malignancies as well. 9,11,14 Considering different cancers present with the common feature of malignant proliferation, we hypothesized that the functions of circ-PVT1 on promoting cancer cell proliferation and suppressing apoptosis might also be existed in EOC cells. As to EOC, several studies have revealed that PVT1 (wherein circ-PVT1 derives from) functions as an oncogene through promoting cell proliferation and reducing apoptosis in EOC cells.…”

Section: Introductionmentioning

confidence: 99%

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Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

Sun

Luo

Gao

2020

J of Obstet and Gynaecol

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Aim This study aimed to investigate the influence of circular RNA PVT1 (circ‐PVT1) on epithelial ovarian cancer (EOC) cell proliferation and apoptosis, more importantly, to identify the target microRNAs (miRNA) of circ‐PVT1 in EOC. Methods Circ‐PVT1 expression in EOC cell lines and nonmalignant control cells was detected. Cell proliferation, apoptosis and candidate target miRNA (miR‐149, miR‐183 and miR‐194) expressions were detected in circ‐PVT1 overexpression treated CAOV3 cells and circ‐PVT1 knock‐down treated SKOV3 cells. Furthermore, miR‐149 overexpression and miR‐149 knock‐down plasmids were transfected into circ‐PVT1 dysregulated CAOV3 cells and SKOV3 cells, respectively, and cell proliferation as well as apoptosis were detected. Results Circ‐PVT1 expression was increased in human EOC cell lines (CAOV3, SKOV3, SNU119 and OVCAR3) compared to human normal ovary surface epithelial cell line (HOSEpiC). In SKOV3 cells, cell proliferation was reduced at 48 and 72 h but cell apoptosis rate was increased at 48 h by circ‐PVT1 knock‐down. In CAOV3 cells, cell proliferation was increased at 48 and 72 h but cell apoptosis rate was decreased at 48 h by circ‐PVT1 overexpression. Besides, circ‐PVT1 negatively regulated miR‐149 but not miR‐183 or miR‐194 in SKOV3 and CAOV3 cells. Rescue experiments showed that miR‐149 knock‐down increased cell proliferation but decreased apoptosis in circ‐PVT1 knock‐down treated SKOV3 cells, while miR‐149 overexpression reduced cell proliferation but enhanced apoptosis in circ‐PVT1 overexpression treated CAOV3 cells. Conclusion Circ‐PVT1 enhances cell proliferation but inhibits cell apoptosis through sponging miR‐149 in EOC cells, which suggests that circ‐PVT1 may serve as a treatment target in EOC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

Sun

Luo

Gao

2020

J of Obstet and Gynaecol

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“…Circular RNAs (circRNAs), a category of endogenous RNAs united by a structure of closed‐loop without a 5ʹ‐3ʹ polarity, are a promising class of non‐coding RNAs capable of regulating transcriptional or posttranscriptional gene expression via functioning as microRNAs (miRNAs) sponges . Several individual circRNAs have been revealed to play essential roles in osteosarcoma pathogenesis, such as regulating cancer cell cycle, cell proliferation, and chemoresistance, and serving as prognostic biomarker in osteosarcoma patients . CircRNA La‐related RNA‐binding protein 4 (circ‐LARP4) is a novel circRNA derived from the LARP4 gene, a gene encoding La‐related RNA‐binding protein that is capable of regulating cancer cell migration and invasion .…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7] Several individual circRNAs have been revealed to play essential roles in osteosarcoma pathogenesis, such as regulating cancer cell cycle, cell proliferation, and chemoresistance, and serving as prognostic biomarker in osteosarcoma patients. [8][9][10] CircRNA La-related RNA-binding protein 4 (circ-LARP4) is a novel circRNA derived from the LARP4 gene, a gene encoding Larelated RNA-binding protein that is capable of regulating cancer cell migration and invasion. 11 Furthermore, it is reported that circ-LARP4 could inhibit cancer cell proliferation and invasion in other cancers apart from osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA‐424 in osteosarcoma

Shen

et al. 2019

Clinical Laboratory Analysis

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Background This study aimed to evaluate the association of circular RNA La‐related RNA‐binding protein 4 (circ‐LARP4) with clinical features and prognosis in osteosarcoma patients, and further explore its effect on chemosensitivity in osteosarcoma cells. Methods Seventy‐two osteosarcoma patients with Enneking stage IIA‐IIB who underwent resection were consecutively enrolled, and then, tumor tissues and non‐tumor tissues were obtained. Circ‐LARP4 in tumor tissue/non‐tumor tissue was detected by quantitative polymerase chain reaction. After circ‐LARP4 overexpression and negative control overexpression plasmid transfection, relative cell viability (%) was evaluated by Cell Counting Kit‐8 in MG63 cells treated by different concentrations of cisplatin, methotrexate, and doxorubicin, and IC50 was calculated. Results Circ‐LARP4 was downregulated in tumor tissue compared with non‐tumor tissue and had a good value in distinguishing tumor tissue from non‐tumor tissue with an area under curve of 0.829 (95% CI: 0.762‐0.859). Meanwhile, tumor circ‐LARP4 was negatively correlated with the Enneking stage. After resection, circ‐LARP4 high expression patients showed an increased tumor cell necrosis rate to adjuvant chemotherapy compared to circ‐LARP4 low expression patients, and circ‐LARP4 high expression correlated with prolonged disease‐free survival and overall survival. In vitro experiments revealed that circ‐LARP4 overexpression elevated the chemosensitivity of MG63 cells to cisplatin and doxorubicin but not methotrexate, with decreased cisplatin IC50 and doxorubicin IC50 concentrations than negative control. Besides, miR‐424 overexpression attenuated the chemosensitivity in circ‐LARP4 overexpression‐treated MG63 cells. Conclusion Circ‐LARP4 high expression correlates with decreased Enneking stage and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging miR‐424 in osteosarcoma.

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Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR‐1270 inhibition

et al. 2019

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Circular RNAs (circRNAs) have recently emerged as essential regulators in carcinogenesis and cancer progression. Previous studies have shown that Cdr1as functions as a microRNA (miRNA) sponge in various cancer types. However, the role of Cdr1as in cisplatin chemosensitivity in bladder cancer remains unclear. Here, we used real‐time PCR to examine miRNA and gene expression in bladder cancer tissues and cell lines. The abilities of Cdr1as and its downstream regulatory molecules to induce apoptosis and promote cisplatin‐induced chemosensitivity of bladder cancer cells were determined by flow cytometry and cell counting kit. Bioinformatic analysis was utilized to predict potential miRNA target sites, and biotin‐coupled miRNA capture, biotin‐coupled probe pull‐down assay, and RNA fluorescent in situ hybridization were used to study the interaction between Cdr1as and target miRNAs. Dual‐luciferase reporter assay was also used to validate the target genes of miRNAs. The expression level of apoptotic protease‐activating factor 1 (APAF1) in bladder cancer cells was identified via western blot. Finally, the sensitivity of Cdr1as to cisplatin chemotherapy in nude mice xenografts was evaluated in terms of the size, volume of tumors, and the survival of mice. We report that Cdr1as induced the apoptosis and enhanced the cisplatin chemosensitivity of bladder cancer cells both in vitro and in vivo . Silencing of APAF1 reduced the sensitivity of bladder cancer cells to cisplatin chemotherapy. Furthermore, Cdr1as could directly sponge miR‐1270 and abolish its effect on APAF1. Our study verified that Cdr1as exerts a cisplatin‐chemosensitization effect on bladder cancer cells through the Cdr1as/miR‐1270/APAF1 axis. This newly identified axis may be a potential therapeutic target for bladder cancer patients.

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Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1

Cited by 227 publications

References 50 publications

Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

Circular RNA PVT1 enhances cell proliferation but inhibits apoptosis through sponging microRNA‐149 in epithelial ovarian cancer

Circular RNA LARP4 correlates with decreased Enneking stage, better histological response, and prolonged survival profiles, and it elevates chemosensitivity to cisplatin and doxorubicin via sponging microRNA‐424 in osteosarcoma

Circular RNA Cdr1as sensitizes bladder cancer to cisplatin by upregulating APAF1 expression through miR‐1270 inhibition

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