hsa_circ_0000745 promotes cervical cancer by increasing cell proliferation, migration, and invasion

Abstract

Circular RNAs (circRNAs) participate in gene regulation and malignant tumor progression, including uterine cervical cancer (CC). In this study, the expression profile of circRNAs in CC was detected using circRNA microarrays. Then, we selected hsa_circ_0000745 for further examination from the significantly dysregulated circRNAs.Proliferation assays, Transwell assays, quantitative reverse transcription polymerase chain reaction, western blot analysis and tumorigenesis tests in vivo were used to validate the role of hsa_circ_0000745 in CC. hsa_circ_0000745 was upregulated in CC, and its level positively correlated with the level of its linear messenger RNA isoform.Patients with poorly differentiated tumors or vascular/lymphatic invasion presented higher expression of hsa_circ_0000745. The role of hsa_circ_0000745 was illuminated by knocking down hsa_circ_0000745 in CC cells, and the results revealed that reducing hsa_circ_0000745 inhibited cell proliferation, migration, and invasion in CC by upregulating E-cadherin (E-cad) expression. In summary, as a tumor promoter in CC, hsa_circ_0000745 enhances the cell's ability to proliferate, migrate, and invade by reducing the expression of E-cad. hsa_circ_0000745 is a candidate target for the treatment of CC in the clinic. K E Y W O R D Scervical cancer, circular RNA, E-cadherin., hsa_circ_0000745, squamous cell carcinoma

Downregulated hsa_circ_0077837 and hsa_circ_0004826, facilitate bladder cancer progression and predict poor prognosis for bladder cancer patients

“…Of them, Liu Y et al reported that circular RNA hsa_circ_0008039 promotes breast cancer cell proliferation and migration by modulating miR‐432‐5p/E2F3 axis and hence may be a potential therapeutic target 42 . Huang et al argued that hsa_circ_000074, as a tumor promoter in CC, enhances the cellʹs ability to proliferate, migrate, and invade by reducing the expression of E‐cad and is a candidate target for the therapy of CC in the clinic 43 . It has been confirmed that hsa_circ_0001946 has been also reported to be extremely downregulated in ESCC tissues by Fanʹs teams 44 and in NSCLC samples by Huangʹs group 45 using another microarray platform and RNA sequencing technology, which confirms the accuracy of our microarray result and potentially implies the crucial role of circ_0001946 in the development of BC as well.…”

Circ_0000527 promotes the progression of retinoblastoma by regulating miR-646/LRP6 axis

“…Accumulating experiments indicate that circRNAs can function as biomarkers for cancer diagnosis and potential therapeutic targets [5]. For instance, circ_0000745 enhances cervical cancer (CC) cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) [6]; circ_0058124 facilitates the progression of papillary thyroid carcinoma by modulating the NOTCH3/GATAD2A axis [7]; circ-SERPINE2 up-regulates the expression of YWHAZ and promotes the progression of gastric cancer [8]. However, the researches on expression function and mechanism of circRNA in RB are relatively rare.…”

Circular RNAs: Novel biomarkers for cervical, ovarian and endometrial cancer (Review)

“…Ding et al (49) demonstrated that circ-ATP8A2 was upregulated in cervical cancer tissues and cell lines, and further confirmed that high levels of circ-ATP8A2 were associated with a higher FIGO stage, positive lymph node invasion and myometrial invasion. In addition, has-circ-u0000745 was upregulated in cervical cancer tissues and cell lines, which was found to be correlated with various clinicopathological features, such as poorly differentiated tumors and positive vascular/lymphatic invasion (45). Another circRNA, circ_0005576, has been associated with a higher pathological stage and lymph node metastasis (50).…”

“…Gao et al (44) conducted a high-throughput microarray study using four pairs of cervical cancer and adjacent noncancerous tissues, revealing 19 downregulated and 26 upregulated circRNAs in cervical cancer. Jiao et al (45) studied circRNA expression profiles using microarray analysis, and found that 178 circRNAs were differentially expressed between cervical cancer and matched normal cervical tissues, of which 101 were downregulated and 77 were upregulated. By classifying the 77 upregulated circRNAs, they also identified 68 exonic, 3 intronic, 1 antisense and 5 intragenic circRNAs in cervical cancer tissues, as well as 101 downregulated circRNAs (including 81 exonic, 13 intronic, 3 antisense and 4 intragenic variants).…”

“…Another circRNA, has-circ-0000745, was revealed to be upregulated in patients with cervical cancer, and high expression levels were associated with poorly differentiated tumors or vascular/lymphatic invasion. Knocking down hsa_circ_0000745 was found to upregulate E-cadherin expression, inhibiting the proliferation, migration and invasiveness of cervical cancer cells, indicating a potential target for cervical cancer treatment (45). Ding et al (49) revealed that circ-ATP8A2, which is highly expressed in cervical cancer specimens and cell lines, enhanced cellular proliferation, migration, invasiveness and apoptosis in cervical cancer.…”