MALAT1 promotes the proliferation and metastasis of osteosarcoma cells by activating the PI3K/Akt pathway

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), one of the first found cancer-associated long noncoding RNAs (lncRNAs), involves in the development and progression of many types of tumors. An aberrant expression of MALAT1 was observed in hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer. However, the exact effects and molecular mechanisms of MALAT1 in osteosarcoma progression are still unknown up to now. Here, we investigated the role of MALAT1 in human osteosarcoma cell lines and clinical tumor samples in order to determine the function of this molecule. In our research, the MALAT1 messenger RNA (mRNA) was highly expressed in human osteosarcoma tissues, and its expression level was closely correlated with pulmonary metastasis. Then, we employed lentivirus-mediated knockdown of MALAT1 in U-2 OS and SaO2 to determine the role of MALAT1 in osteosarcoma cell lines. Lentivirus-mediated MALAT1 small interfering RNA (siRNA) could efficiently downregulated the expression level of MALAT1 in osteosarcoma cell lines. Knockdown of MALAT1 inhibited the proliferation and invasion of human osteosarcoma cell and suppressed its metastasis in vitro and vivo. At the same time, the proliferating cell nuclear antigen (PCNA), matrix metallopeptidase 9 (MMP-9), phosphorylated PI3Kp85α, and Akt expressions were significantly inhibited in MALAT1-deleted cells. These findings indicated that MALAT1 might suppress the tumor growth and metastasis via PI3K/AKT signaling pathway. Taken together, our data indicated that MALAT1 might be an oncogenic lncRNA that promoted proliferation and metastasis of osteosarcoma and could be regarded as a therapeutic target in human osteosarcoma.

Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer

“…MALAT1 is an evolutionarily conserved lncRNA that does not undergo translation into protein (16). Nevertheless, previous findings suggest that MALAT1 regulates the alternative splicing of pre-mRNAs by controlling the expression of serine/arginine splicing factors, while also having a key role in tumorigenesis (27).…”

“…To date, evidence demonstrates that MALAT1 plays a key role in the progression of various cancers, including cervical cancer (15), osteosarcoma (16), breast cancer (17) and colorectal cancer (18). However, the expression and function of MALAT1 are currently unknown in OC.…”

Transcription factor Oct4 promotes osteosarcoma by regulating lncRNA AK055347

“…Previous studies have demonstrated that lncRNAs may exert different effects in osteosarcoma. Metastasis-associated lung adenocarcinoma transcript 1 was reported to promote the proliferation and metastasis of osteosarcoma cells (30). Downregulation of taurine upregulated 1 inhibited osteosarcoma cell proliferation and promoted apoptosis (31).…”

The Role of Long Non-Coding RNAs in Ovarian Cancer

“…As one of the first identified cancer-associated lncRNAs, MALAT1 contributes to the pathogenesis of many types of tumors, including hepatocellular carcinoma, cervical cancer, breast cancer, ovarian cancer, and colorectal cancer [26] . MALAT1 knockdown has suppressed the proliferation and the invasion of human osteosarcoma cell and inhibited its metastasis potential.…”