Inhibition of the long non‐coding RNA UNC5B‐AS1/miR‐4455/RSPO4 axis reduces cervical cancer growth in vitro and in vivo

Abstract

Background: Long non-coding RNAs (lncRNAs) are significant regulatory factors for the initiation and development of numerous malignant tumors, including cervical cancer (CC). The expression of lncRNA unc-5 netrin receptor B antisense RNA 1 (UNC5B-AS1, also known as UASR1) is up-regulated in tissues of cervical squamous cell carcinoma and endocervical adenocarcinoma compared to in normal tissues based on the GEPIA database. In the present study, we explored the functions of UNC5B-AS1 and its underlying mechanism with respect to CC development. Methods: A real-time quantitative polymerase chain reaction was applied for the detection of UNC5B-AS1 expression in CC cells. Cell counting kit-8, colony formation and transwell assays, as well as western blot and flow cytometry analyses, were employed to detect the biological effects of UNC5B-AS1 knockdown on malignant phenotypes of CC cells in vitro. In addition, the combination between microRNA-4455 (miR-4455) and UNC5B-AS1 or R-spondin 4 (RSPO4) was explored by RNA immunoprecipitation, luciferase reporter and RNA pulldown assays. A tumor xenograft nude mice model was established to explore the effect of UNC5B-AS1 depletion or miR-4455 overexpression on tumor growth. Results: UNC5B-AS1 is up-regulated in CC tissues and cells. The knockdown of UNC5B-AS1 inhibits CC cell proliferation, migration and invasion and promotes CC cell apoptosis. Mechanistically, UNC5B-AS1 binds with miR-4455 to up-regulate RSPO4 expression. RSPO4 is targeted by miR-4455 and its expression is negatively regulated by miR-4455 expression. In vivo assays revealed that UNC5B-AS1 depletion or miR-4455 overexpression inhibits tumor growth by regulating RSPO4 expression. Conclusions: Inhibition of UNC5B-AS1/miR-4455/RSPO4 reduces CC growth both in vitro and in vivo, furnishing new insights into molecular studies on UNC5B-AS1 with respect to CC development.

Identification of pyroptosis-related genes and long non-coding RNAs signatures in osteosarcoma

“…The UNC5B-AS1 functions similarly to FOXD2-AS1, and its expression is up-regulated in hepatocellular carcinoma, papillary thyroid cancer, and prostate cancer [ 58 – 60 ]. The silencing of UNC5B-AS1 inhibits tumor growth [ 61 , 62 ], but it has not been reported in osteosarcoma. SENCR has been extensively studied in the vascular smooth muscle cells and endothelial cells [ 63 , 64 ], but recent studies have showed that it also has a role in cancer.…”

Network analysis of long non-coding RNA expression profiles in common warts

“…UNC5B-AS1 , also known as UASR1 , was found to be downregulated in senescent normal oral keratinocytes, [ 47 ]. In contrast, UNC5B-AS1 upregulation increased cell proliferation in breast, cervical, colorectal, oral squamous cell, and papillary thyroid cancers [ 48 , 49 , 50 , 51 , 52 ].…”

The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer

“…MicroRNA-29c inhibits the epithelial-mesenchymal transition in cervical cancer cells, leading to the inhibition of proliferation, invasion and metastasis [74]. The inhibition of the microRNA-4455 axis expression reduces cervical cancer growth in vitro and in vivo [75]. Thus, it appears that calcitriol-dependent increased bioavailability of DDX5 might cause the RNA substrates to be readily processed by the ribonuclease Dicer, enhancing in this way the maturation rate of microRNAs associated with anti-cancer-related functions.…”