LncRNA HOXA-AS3 Sponges miR-29c to Facilitate Cell Proliferation, Metastasis, and EMT Process and Activate the MEK/ERK Signaling Pathway in Hepatocellular Carcinoma

摘要

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with high morbidity and mortality across the world. Recent findings have suggested that long noncoding (lnc)RNA HOXA-AS3 plays an important role in tumorigenesis and metastasis in a variety of cancers. However, the role of lncRNA HOXA-AS3 in the initiation and progression of HCC remains largely unclear. In the present study, HOXA-AS3 was highly expressed in HCC tumor tissues and cell lines. High HOXA-AS3 expression was correlated with low survival of HCC patients. Loss-of-function experiments showed that knockdown of HOXA-AS3 inhibited cell proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT) process, and the mitogen-activated protein kinase/extracellular regulated protein kinase (MEK/ERK) signaling pathway in HCC. Molecular mechanism exploration uncovered that HOXA-AS3 could directly interact with and negatively regulate miR-29c. BMP1 is a downstream target gene of miR-29c, and HOXA-AS3 could regulate BMP1 expression by targeting miR-29c. miR-29c negatively regulated and BMP1 promoted the progression of HCC. Rescue experiments revealed that miR-29c inhibitor could partially counteract the impact induced by HOXA-AS3 knockdown in HCC. Taken together, our study is the first to show the interaction of HOXA-AS3 with miR-29c in facilitating cell proliferation, metastasis, EMT process, and MEK/ERK signaling pathway in HCC.