Bone Abstracts

We found that miR-335 is reduced in SBC-5, a human lung cancer (LC) derived cell lines inducing osteoclast formation by expressing RANKL; reviving miR-335 expression in SBC-5 results in decrease of its proliferation, invasion, migration and clone formation in vitro; reviving miR-335 expression in LC model leads to reduction of bone metastasis (BM) in vivo. It was confirmed that miR-335, inhibiting the formation and activity of osteoclasts and reducing the proliferation of tumor cells by targeting RANKL and insulin-like growth factor-I receptor (IGF-IR) expression, is an important miRNA regulating bone metastasis of lung cancer (LCBM).

MiR-21 level in SBC-5 and its supernatant were found significantly increased, while expression of miR-21 was elevated in serum of LCBM patients. Providing inhibitor of miR-21 attenuates SBC-5 induced osteoclast formation. It suggests high expression of miR-21 in LC may be released into blood circulation and is closely related to BM.

Our data shows changes of miRNA profile (miR-335,miR-21, etc.) occur in some LC cells according to the environment and genetic factors. Abnormally expressed miRNAs could not only be released into blood circulation due to necrosis or secretion of LC cells but also result in abnormal expression of BM related proteins, which make LC cells acquire the characteristic of BM. Arriving bones via blood circulation, those free miRNAs and bone-seeking LC cells interact with osteoclasts/osteoblasts in bone microenvironment and result in osteolytic lesion by destroying balance between bone formation and resorption. Growth factors released from destroyed bone promote growth of LC cells in bone, which cause the osteolytic BM finally. Including miRNAs and their upstream/downstream proteins, the signaling network regulates occurrence and development of LCBM, which may serve as biomarker of diagnosis and target of therapy for LCBM.