The involvement of MALAT1-ALKBH5 signaling axis into proliferation and metastasis of human papillomavirus-positive cervical cancer

Cancer Biol Ther. 2023 Dec 31;24(1):2249174. doi: 10.1080/15384047.2023.2249174.ABSTRACTInfection with high-risk human papillomavirus (HPV), for example, with types 16 and 18, is closely associated with cervical cancer development, which continues to threaten women's health globally. Although HPV oncogenes have been recognized as the main cause of transformation of normal cervical epithelial cells, non-coding RNA could also be involved in the initiation and promotion of cervical cancer development. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented long non-coding RNA (lncRNA), has been previously reported to exert roles in HPV-positive cervical cancer; however, the detailed underlying mechanism has yet to be investigated. In the present study, high expression levels of MALAT1 in HPV-Positive Cervical Cancer cells were confirmed, and silencing MALAT1 resulted in decreased rates of cell proliferation, migration, and invasion, both in vitro and in a zebrafish xenograft tumor model. Moreover, the results obtained showed that silencing MALAT1 led to down-regulation of the N6-methyladenosine (m6A) demethylase ALKBH5 via regulating miR-141-3p expression, which caused a decrease in the expression levels of matrix metalloproteinase 2 (MMP2) and MMP9 expression, thereby suppressing cell migration and invasion. Taken together, the results obtained have suggested that the MALAT-ALKBH5 signaling axis may be activated in HPV-positive cervical cancer cells, ...
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Source Type: research