RETRACTED ARTICLE: Knockdown of circRNA_0007534 suppresses the tumorigenesis of cervical cancer via miR-206/GREM1 axis

Abstract

Background Increasing evidence manifested that circular RNAs (circRNAs) acted as crucial regulators in human cancers by targeting the miRNA/mRNA axis, including cervical cancer (CC). Circ_0007534 was reported to promote CC cell proliferation and invasion by the miR-498/BMI-1 axis. The aim of this study was to explore a novel miRNA/mRNA network underlying circ_0007534 in CC regulation. Methods The quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to examine the levels of circ_0007534, miR-206 and Gremlin1 (GREM1). Cell viability was determined using MTT assay. BrdU and colony formation assays were performed for analyzing cell proliferation. Cell apoptosis was assessed by flow cytometry. The protein levels of GREM1 and apoptotic markers (Bcl-2, Bax, C-Caspase3) were measured via western blot. Cell invasion was detected by transwell assay. The target relationship was analyzed by dual-luciferase reporter assay. The impact of circ_0007534 on CC growth in vivo was ascertained by xenograft assay. Results Circ_0007534 expression was aberrantly increased in CC tissues and cells. Functionally, knockdown of circ_0007534 reduced CC cell growth and invasion but motivated apoptosis. In the mechanism, circ_0007534 targeted miR-206 and its regulatory function was associated with sponging miR-206. Moreover, circ_0007534 was found to regulate GREM1 level by targeting miR-206. The inhibitory effect of si-circ_0007534 on the malignant progression of CC was reversed after GREM1 was overexpressed. Furthermore, circ_0007534 inhibition also reduced tumor growth of CC in vivo partially by regulating miR-206/GREM1 axis. Conclusion These results suggested that knockdown of circ_0007534 promoted the level of miR-206 to induce the expression downregulation of GREM1, consequently inhibiting the progression of CC.

Circ-SFMBT2 drives the malignant phenotypes of esophageal cancer by the miR-107-dependent regulation of SLC1A5

“…The dysregulated circRNAs have been implicated in the regulation of cancer development. For instance, knockdown of circRNA_0007534 suppressed proliferation and accelerated apoptosis in cervical cancer cells [ 21 ]. CircGFRA1 promoted the tumor growth and metastasis of hepatocellular carcinoma [ 22 ], and circNDUFB2 repressed the malignant progression of non-small cell lung cancer [ 23 ].…”

Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways

“…The effect of GREM1 on the prognosis of malignant tumors remains elusive. Some studies have linked high GREM1 expression to poor prognosis in several malignancies, including ER-negative breast cancer [ 16 ], cervical cancer [ 61 ], ex-trahepatic cholangiocarcinoma [ 62 ], basal cell carcinoma [ 63 ] and renal cell carcinoma [ 64 ]. In CRC, high GREM1 protein expression has been associated with low tumor stage and extended survival [ 20 ].…”

Biological functions, mechanisms, and clinical significance of circular RNA in pancreatic cancer: a promising rising star

“…These results suggest that hsa_circ_0000677 might play a role in promoting carcinogenesis and development in PC cells. has_circ_0007534, located on chromosome 17, is a circRNA produced by exons 4 and 7 that is abnormally expressed in colorectal cancer and cervical cancer [ 76 , 77 ]. Hao et al found that this circRNA is also highly expressed in PC tissues and cells [ 78 ].…”