N 6 -Methyladenosine Modification of ANLN Enhances Hepatocellular Carcinoma Bone Metastasis.

Bones are categorized as the second most prevalent location of extra-hepatic metastasis in Hepatocellular Carcinoma (HCC), which is linked to an extremely poor prognosis due to limited therapeutic options. N-methyladenosine (mA) is a prominent modification involved in HCC, but the exact mechanisms on how mA modifications induce HCC bone metastases (BM) remain unclear. The key modulators responsible for the abundant mA RNA modification-induced HCC BM was found to be the and . The expression of Anillin actin-binding protein () was dramatically higher in HCC with BM tissues, and its messenger RNA (mRNA) stability was enhanced via mA epitranscriptomic regulation by and . High and expression along with nuclear protein was clinically correlated with BM in HCC patients. Furthermore, HCC BM was attributed to over-expression of nuclear forming a transcriptional complex with which enhanced transcriptional activity to activate the mTORC1 pathway, therefore increased the expression of and disproportionated expression in bone microenvironment leading to malignant neoplasms invade bone tissue. In addition, inhibition of mA modification by DZNeP attenuated HCC BM. This data provides meaningful understanding of the modulation and association of mA epitranscriptomic-regulated BM in HCC, and moreover, defines potentially valuable therapeutic targets.