circ_0075943 Dominates the miR-141-3p/AK2 Network to Support the Development of Breast Carcinoma

Abstract

Background. Breast cancer (BC) progression is related to the disorder of circular RNAs (circRNAs). This study aims to characterize the role of circ_0075943 in BC. Methods. Real-time fluorescent quantitative PCR (real-time PCR) technology was implemented to investigate circ_0075943, AK2 mRNA, and microRNA-141-3p levels. MTT, colony formation method, Transwell, and flow cytometry technique were adopted to investigate cell function. The connection between miR-141-3p and circ_0075943 or AK2 was confirmed by the dual-luciferase reporter gene or RNA immunoprecipitation (RIP). The influence on circ_0075943 in vivo was confirmed by animal experiments. Results. circ_0075943 was augmented in BC cell lines and tumor specimens. Dwindling of circ_0075943 could dramatically suppress the phenotype of BC cells and induce apoptosis. MiR-141-3p is a target of circ_0075943, and its repression largely reverses the influence of knocking down circ_0075943 on cell behavior. Moreover, AK2, as a target of miR-141-3p, is augmented in BC cells and specimens. AK2 overexpression could restore the phenotype of BC cells blocked by miR-141-3p redevelopment. Moreover, knocking down circ_0075943 could suppress the growth of tumors in vivo. Conclusion. The abnormal regulation of circ_0075943 participates in part of the expansion of BC by dominating the miR-141-3p/AK2 regulatory network.

Interactions between circRNAs and miR-141 in Cancer: From Pathogenesis to Diagnosis and Therapy

“…Another study discovered that hsa_circ_0075943 is overexpressed in BC cell lines and tissue specimens [95]. Hsa_circ_0075943 has multiple binding sites for miR-141-3p, which increases AK2 mRNA and protein levels in BC cells and tumor samples [95].…”

“…Another study discovered that hsa_circ_0075943 is overexpressed in BC cell lines and tissue specimens [95]. Hsa_circ_0075943 has multiple binding sites for miR-141-3p, which increases AK2 mRNA and protein levels in BC cells and tumor samples [95]. AK2 is an isoform of adenylate kinase, a critical enzyme in the cellular homeostasis of adenine nucleotides, which is involved in malignant transformation by the regulation of metabolism of cancer cells, metabolic signaling, invasion and migration [117].…”

“…AK2 is an isoform of adenylate kinase, a critical enzyme in the cellular homeostasis of adenine nucleotides, which is involved in malignant transformation by the regulation of metabolism of cancer cells, metabolic signaling, invasion and migration [117]. The knockout of hsa_circ_0075943 was able to inhibit the malignant behavior of BC by increasing the miR-141-3p level, suppressing the growth of cancer cells and inducing apoptosis, which may be crucial in the development of novel therapies for this cancer [95].…”

Adenylate kinase 2 is a biomarker related to the prognosis of glioma and the immune microenvironment

“…In addition, in lung adenocarcinoma, AK2 was overexpressed, and high AK2 expression was linked to tumor development and indicated poor prognoses in patients with pulmonary adenocarcinoma 13,14 . It was also reported that AK2 plays a role in hepatocellular carcinoma (HCC), breast cancer, and cervical cancer 15–17 . Although AK2 is related to several malignancies, little is known about the precise underlying mechanisms and its potential cancer‐driving roles, particularly in glioma.…”

“… 13 , 14 It was also reported that AK2 plays a role in hepatocellular carcinoma (HCC), breast cancer, and cervical cancer. 15 , 16 , 17 Although AK2 is related to several malignancies, little is known about the precise underlying mechanisms and its potential cancer‐driving roles, particularly in glioma. Thus, it requires more investigation to determine the predictive value and potential roles of AK2 in glioma.…”