Mechanism for Bioactive Nanomaterial circ0024831 Regulation of Staphylococcal Nuclease Domain Containing 1 via RNA Methylation Recognition in Osteosarcoma

Abstract

Bioactive nanomaterial circular RNA (circRNA) is an important non-coding RNA with a strong specificity, stable structure and high expression abundance. It can affect many diseases and physiological processes and may become a new way of disease diagnosis and targeted therapy. Recent studies have shown that Staphylococcal Nuclease Domain-Containing Protein 1 (SND1) can recognize N6-methyladenine (M6A) modified mRNA and regulate target mRNA stability. It can then control the expression of a series of downstream genes. However, whether SND1 can directly combine with circRNA and regulate its stability and function are new issues to be discussed. Results showed bioactive nanomaterial circ0024831 could directly bind to the Tudor domain of SND1 in the cytoplasm to block the recognition of SND1 to M6A modified RNA thus reducing the stability of downstream target gene mRNA and inhibiting the expression of downstream regulatory proteins. The down-regulation of circ0024831 expression in osteosarcoma cells relieved inhibition of SND1 which lead to change of tumor-related gene expression profile, promoting the occurrence and development of osteosarcoma.

Screening and identifying of biomarkers in early colorectal cancer and adenoma based on genome-wide methylation profiles

“…Our results similarly indicated that ZNF471 methylation level was higher in CRC and colorectal adenoma than the normal group which suggested that our results for ZNF471 appear consistent with the above previous study and indicate this gene might display good diagnostic value as a tumor suppressor for both colorectal cancer and adenomas. As an N6-methyladenosine (m6A) reader, SND1 is associated with methylation and can modify mRNA and regulate target mRNA stability [ 20 ]. SND1 expression was increased in tumors such as bladder cancer [ 21 ], glioma [ 22 ], and ovarian cancer [ 23 ] and correlated with proliferation and metastasis as well as chemoresistance.…”

N6-methyladenosine (m6A) modification in osteosarcoma: expression, function and interaction with noncoding RNAs – an updated review

“…Recent studies have shown that SND1 can bind to circ0024831. Overexpression of SND1 reverses the negative regulatory effect of circ0024831 on osteosarcoma and promotes the progression of osteosarcoma [ 63 ].…”

“… [ 64 ] circ0024831 SND1 Oncogene circ0024831 target SND1 COX-2/PGE2 Proliferation↑ SND1 can recognize m6A-modified mRNA and regulate target mRNA stability. [ 63 ] lncRNA DANCR METTL3 Oncogene METTL3 regulate DANCR / Proliferation↑, invasion, and metastasis↑ METTL3 contributes to progression by increasing DANCR mRNA stability via m6A modification [ 51 ] PVT1 ALKBH5/YTHDF2 Oncogene ALKBH5/YTHDF2 regulate PVT1 / Proliferation↑ ALKBH5 demethylates PVT1, which is subsequently recognized by YTHDF2 and inhibits its degradation [ 59 ] FOXD2-AS1 WTAP Oncogene WTAP regulate FOXD2-AS1 FOXM1 Proliferation↑, invasion and metastasis↑ WTAP enhanced the stability of FOXD2-AS1 [ 54 ] …”

“…In addition, circRNAs regulate m6A modification. A recent study revealed that the nanomaterial circ0024831 could directly bind to the Tudor domain of SND1 in the cytoplast to block the recognition of m6A-modified RNA by SND1 and inhibit the occurrence and development of osteosarcoma [ 63 ]. circ-CTNNB1 is highly expressed in osteosarcoma.…”