New Insights into the Molecular Mechanisms Underlying the Malignant Transformation of Endometriosis: BRAF-activated Non-Coding RNA (BANCR) Promotes Activity of the Mirna-612/Cpne3 Pathway

Research question Does LncRNA BANCR promote the malignant transformation of endometriosis by activating the miRNA-612/CPNE3 pathway? Design We determined the expression patterns of BANCR, miRNA-612 and CPNE3 in normal endometrium (NE), eutopic endometrium (euEM) from endometriosis, eutopic endometrium (MEU) or malignant tissues (MTE) from endometriosis-associated ovarian cancer (EAOC). Based on primary normal and eutopic endometrial stromal cells (NESCs and EESCs), the regulatory relationships between BANCR, miRNA-612 and CPNE3 and the potential mechanisms that promote the malignant transformation of endometriosis were elucidated both in vitro and in vivo. Results The expression levels of BANCR and CPNE3 were lowest in NE, significantly increased in euEM (p < 0.05) and exhibited a further significant increase in MEU (p < 0.05). During the malignant transformation of endometriosis, the expression levels of BANCR and CPNE3 were significantly up-regulated (p < 0.05), while those of miR-612 were significantly down-regulated (p < 0.05). miRNA-612 was found to target BANCR and CPNE3. The overexpression/knockdown of BANCR in NESCs/EESCs upregulated/downregulated the expression of CPNE3 and promoted/prevented cell proliferation and migration, respectively; these effects were reversed by miRNA-612 mimics/inhibitor. These changes were all statistically significant; p < 0.05). In vivo experiments revealed that BANCR significantly increased the survival of subcutaneous endometrial cells by regulating miRNA-612/CPNE3 (p < 0.05). Conclusion The expression of BANCR gradually increased with the progression of endometriosis during malignant transformation and promoted the proliferation and migration of endometrial cells via the miRNA-612/CPNE3 pathway. BANCR may represent a novel target for monitoring the malignant transformation of endometriosis.