Hsa_circ_0020095 Promotes Oncogenesis and Cisplatin Resistance in Colon Cancer by Sponging miR-487a-3p and Modulating SOX9

Abstract

ObjectivesColon cancer (CC) currently ranks as the third most common human cancer worldwide with an increasing incidence and a poor prognosis. Recently, circular RNAs have been reported to regulate the progression of diverse human cancers. However, the role of circRNA hsa_circ_0020095 in CC remains largely unclear.MethodsExpression levels of the related circRNAs, microRNAs and mRNA in CC tissues and cells were determined. The impacts of circ_0020095 or miR-487a-3p on CC cells were examined at the indicated times after transfection. Meanwhile, a luciferase-reporter experiment was employed to validate the interplay between miR-487a-3p and circ_002009695 or SOX9. Moreover, the in vivo tumor growth assay was applied to further evaluate the effects of circ_0020095 knockdown on CC progression.ResultsWe demonstrated that circ_0020095 was highly expressed in CC tissues and cells. The proliferation, migration, invasion, and cisplatin resistance of CC were suppressed by silencing circ_0020095 in vitro and in vivo or by ectopic expression of miR-487a-3p in vitro. Mechanistically, circ_0020095 could directly bind to miR-487a-3p and subsequently act as a miR-487a-3p sponge to modulate the activity by targeting the 3′-UTR of SOX9. Interestingly, overexpression of circ_0020095 dramatically reversed the suppressive effects of miR-487a-3p mimics on CC cells.ConclusionCirc_0020095 functions as an oncogene to accelerate CC cell proliferation, invasion, migration and cisplatin resistance through the miR-487a-3p/SOX9 axis, which could be a promising target for CC treatment.

New Molecular Mechanisms and Clinical Impact of circRNAs in Human Cancer

“…Very recently, several research groups have uncovered altered expressions of circRNAs in CRC, which, by supporting chemoresistance, induce cell proliferation, invasion, and migration through different mechanisms, the most common being that of miRNA sponging. For example, circ_0020095 was found to be highly present in CRC tissues and cells affecting proliferation, migration, invasion, and cisplatin resistance [55]. Mechanistically, circ_0020095 bound to miR-487a-3p, increasing SOX9 expression [55].…”

“…For example, circ_0020095 was found to be highly present in CRC tissues and cells affecting proliferation, migration, invasion, and cisplatin resistance [55]. Mechanistically, circ_0020095 bound to miR-487a-3p, increasing SOX9 expression [55]. Xu and colleagues showed the interaction between circ-FBXW7 and miR-18b-5p in CRC cell lines [56].…”

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer

“…MACC1 is a transcription factor which, via HGF/cMET axis, is involved in EMT in CRC [ 156 ]. Hsa_circ_0020095 positively regulates the transcription factor SOX9 (sex-determining region Y (SRY)-box 9 protein) via sponging miR-487a-3p [ 157 ]. SOX9 leads to increased cell invasiveness and metastasis as well as activation of EMT by increasing S100P, a calcium-binding protein from the S100 protein family [ 158 ].…”

“…Hsa_circ_0071589 is the next circRNAs with a complex mechanism involving the inhibition of the expression of another miR-526b-3p together with miR-600 [ 121 , 213 ] Hsa_circ_0071589 might regulate cisplatin resistance in CRC targeting oncogene KLF12 (Krüppel-like factor 12) by miR-526b-3p [ 213 ]. Hsa_circ_0020095 is another circRNA with investigated effect on cisplatin treatment in CRC cells [ 157 ]. Sun et al, 2021 [ 157 ] reported that the circ_0020095 resistance towards cisplatin is dose- and time-dependent.…”

Bioinformatics Analysis: The Regulatory Network of hsa_circ_0007843 and hsa_circ_0007331 in Colon Cancer

“…The prognosis of patients with CC is still not very ideal, so it is necessary to find new treatments as soon as possible [3]. In recent years, a large number of studies have found that circular RNA (circRNA) plays an important role in the occurrence, development, metastasis, and invasion of CC [4][5][6][7][8][9][10] and can also be used as biomolecule markers for the diagnosis and prognosis [11]. circRNA is a new type of endogenous noncoding RNA, without a 5′-end cap and 3'-end poly (A) tail structure, showing a covalently closed loop [12].…”