Circular RNA circPRMT5 is upregulated in breast cancer and is required for cell proliferation and migration.

BACKGROUND: To evaluate the role of cyclic protein arginine methyltransferase 5 (circPRMT5) in the occurrence and development of breast cancer (BC). METHODS: A total of 90 BC patients who underwent radical mastectomy and 40 age-matched healthy female controls were recruited in the Second People's Hospital of China Three Gorges University, Yichang Second People's Hospital from 2017 to 2020. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to detect the expression levels of circPRMT5 in BC tissues, serum, normal breast cell line (MCF-10A), and BC cell line (T47D, MCF-7, BT549, Hs-578T, and MDA-MB-231, MDAMB-468). The associations between circPRMT5 expression level and age, tumor size, degree of differentiation, TNM stage, distant metastasis, estrogen receptor (ER) or progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status were analyzed. BC cell lines with circPRMT5 knockdown or overexpression were subject to CCK-8 cell proliferation assay, and transwell cell invasion/migration assay. RESULTS: CircPRMT5 expression in BC tissue was higher than that in adjacent normal breast tissue. Consistently, the expression level of circPRMT5 was also elevated in serum samples collected from BC patients when compared with healthy controls. And in multiple breast cancer cell lines, circPRMT5 was upregulated as compared to normal breast epithelial MCF-10A cells. CircPRMT5 expression level was correlated with tumor size, TNM stage, lymph node metastasis distant metastasis, but no correlation was observed with ER, PR, HER2 status. Overexpression of circPRMT5 promoted the proliferation, invasion, and migration of MCF7 cells; while the knockdown of circPRMT5 inhibited cell proliferation, invasion, and migration. DISCUSSION: CircPRMT5 seems to act as an oncogene in the progression of BC. Our data suggest that CircPRMT5 may be used as a biomarker for the diagnosis, prognosis evaluation, and targeted therapy of breast cancer.

Treatment of bladder cancer by geoinspired synthetic chrysotile nanocarrier-delivered circPRMT5 siRNA.

BACKGROUND: Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. METHODS: Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. RESULTS: The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5's half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/si-circPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression. CONCLUSION: The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Circular RNA CircPRMT5 Accelerates Proliferation and Invasion of Papillary Thyroid Cancer Through Regulation of miR-30c/E2F3 Axis.

BACKGROUND: The role of circular RNA (circRNA) in papillary thyroid cancer (PTC) is largely unknown. This study aims to determine the function and mechanism of circPRMT5 in the regulation of PTC development. METHODS: PTC tissues and cell lines were used to determine circPRMT5 expression via quantitative real-time polymerase chain reaction. Small interfering RNA (siRNA) was utilized to knock down circPRMT5. Proliferation was analyzed through CCK8 and colony formation assays. Transwell assay was performed to determine cell migration and invasion. Luciferase assay and RIP assay were carried out to analyze the interaction between circPRMT5 and miR-30c. RESULTS: CircPRMT5 expression was upregulated in PTC tissues and cell lines. And circPRMT5 level was positively linked with advanced stage and lymph node metastasis. CircPRMT5 knockdown inhibited proliferation, migration and invasion while inducing apoptosis. CircPRMT5 worked as a competing endogenous RNA for miR-30c. By inhibiting miR-30c, circPRMT5 promoted the expression of E2F3. CONCLUSION: Our findings demonstrate that circPRMT5 acts as an oncogenic circRNA to promote PTC progression via regulating miR-30c/E2F3 axis.

CircPRMT5 circular RNA promotes proliferation of colorectal cancer through sponging miR-377 to induce E2F3 expression.

CircPRTM5 is associated with cell proliferation and migration in many kinds of malignancies. However, the functions and mechanisms of CircPRTM5 in CRC progression remain unclear. We explored the role and the mechanisms of CircPRTM5 in the development of CRC. Tissues of CRC patients and matched adjacent non-tumour tissues were collected to evaluate the expression of CircPRTM5. The expression of CircPRTM5 in CRC tissues was significantly higher than that in adjacent tissues. The biological functions of CircPRTM5 in CRC were determined by overexpression and down-regulation of CircPRTM5 in CRC cells in vitro and in vivo. The results indicate that knockdown of CircPRTM5 can significantly inhibit the proliferation of CRC cells. The potential mechanisms of CircPRTM5 in CRC development were identified by RT-qPCR, Western blotting analysis and luciferase reporter assay. CircPRTM5 competitively regulates the expression of E2F3 by capillary adsorption of miR-377. CircPRMT5 regulates CRC proliferation by regulating the expression of E2F3, which affects the expression of the cell cycle-associated proteins cyclinD1 and CDK2. CircPRTM5 exerts critical regulatory role in CRC progression by sponging miR-377 to induce E2F3 expression.

Role and mechanism of circular RNA protein arginine methyltransferase 5 in proliferation, migration of colorectal cancer cells / 中华消化杂志

Objective To evaluate the role of circular RNA protein arginine methyltransferase 5 (circPRMT5) in the genesis and progression of colorectal cancer.Methods From January 2013 to December 2017,96 patients with colorectal cancer who underwent radical resection in Department of General Surgery,Jiading District Central Hospital Affiliated to Shanghai Medical College of Health were collected.The expression of circPRMT5 in colorectal cancer tissues was examined by real-time polymerase chain reaction (RT-PCR).The correlation between circPRMT5 expression level and age,gender,tumor size,tumor location,pathological differentiation,TNM stage,lymph node metastasis of patients with colorectal cancer was analyzed.The SW620 and LOVO cells were divided into control group,circPRMT5-lenti group and circPRMT5-shRNA-lenti group according to different interventions.The effects of circPRMT5 expression level on viability,apoptosis,mitochondrial membrane potential and migration of SW620 and LOVO cells were detected.The influence of circPRMT5 expression level on E-cadherin,Slug,N-cadherin and vimentin was determined by Western blotting method.The potential target miRNA of circPRMT5 was predicted by Starbase V2.0.Student's t test,analysis of variance and chi-square test were performed for statistical analysis.Results The results of RT-PCR showed that the expression of circPRMT5 in colorectal cancer tissues was higher than that of adjacent cancer tissues (2.167 ± 0.345 vs.1.103 ± 0.144),and the difference was statistically significant (t =26.847,P ＜ 0.01).The circPRMT5 expression level was positively correlated with tumor size,TNM stage,lymph node metastasis and distant metastasis (x2 =6.010,10.971,5.321 and 6.272,all P ＜0.05).The upregulation of circPRMT5 expression could promote proliferation and migration of SW620 and LOVO cells.The circPRMT5 downregulation could inhibit cell proliferation,induce apoptosis and decrease mitochondrial membrane potential.The results of Western blotting indicated that,compared with those of control group,the expression of Slug,N-cadherin and vimentin increased in circPRMT5-1enti group (1.023 ±0.038 vs.2.105 ±0.042,1.051 ±0.309 vs.2.277 ± 0.111,1.055 ± 0.040 vs.2.002 ± 0.537,respectively),however the expression of E-cadherin decreased (2.074 ± 0.214 vs.0.627 ± 0.023),and the differences were statistically significant (t =31.817,22.065,14.536 and 9.148,all P ＜ 0.01).Compared with the control group,the expression of Slug,N-cadherin and vimentin decreased in circPRMT5-shRNA-lenti group (1.023 ± 0.038 vs.0.585 ± 0.023,1.051 ± 0.309 vs.0.616 ± 0.043,1.055 ±0.040 vs.0.537 ±0.022),while the expression of E-cadherin increased (2.074 ± 0.214 vs.2.756 ± 0.148),and the differences were statistically significant (t =-13.795,-14.252,-11.794 and-13.116,all P ＜ 0.05).A total of 21 miRNAs might have potential binding sites with circPRMT5 predicted by Starbase V2.0 software.The expression of miRNA4735-3p,miRNA202-3p,miRNA326,let-7i-5p and miRNA4500 was negatively correlated with circPRMT5 expression in both SW620 and LOVO cells confirmed by RT-PCR.Conclusion CircPRM75 is an important oneogenic gene in the genesis and progress of colorectal cancer,and may have certain potential application prospect in the research and development for colorectal cancer.