MALAT1 promotes epithelial-mesenchymal transition of pancreatic cancer cells through the miR-141-5p-TGF-ß-TGFBR1/TGFBR2 axis.

Abstract

Pancreatic cancer (PC) is one of the leading causes of cancer deaths, associated with a high risk of metastasis and mortality. The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is highly expressed in multiple types of tumour tissues and may be associated with the growth of PC cells. In this study, we aimed to assess the role and possible mechanisms of MALAT1 in PC progression. Expression of MALAT1 was studied by quantitative real-time polymerase chain reaction (qRT-PCR) in PC tissues. The dual-luciferase assay was performed to validate binding between MALAT1 and miR-141-5p in HEK293 cells. Western blot analysis was performed to examine the expression of transforming growth factor beta (TGF-β) and its receptors, TGFBR1 and TGFBR2. Invasiveness and migration of cultured PANC-1 cells were studied using transwell invasion and migration assays, respectively. A high level of miR-141-5p and low level of MALAT1 were detected in PC tissues, and the level of MALAT1 was shown to significantly correlate with tumour growth and metastasis. In HEK293 cells, miR-141-5p overexpression inhibited the expression of TGFBR1 and TGFBR2, and this inhibition was reversed by overexpression of MALAT1. In PANC-1 cells, MALAT1 was shown to act as a competing endogenous RNA, as the direct target of miR-141-5p. Furthermore, in PANC-1 cells, miR-141-5p overexpression suppressed TGF-induced epithelial-mesenchymal transition (EMT), cell migration, and cell invasion through direct binding to the 3'UTR of TGFBR1 and TGFBR2. Our results indicate that, in PC cells, miR-141-5p suppresses TGFBR1 and TGFBR2 expression and further inhibits TGF-β-induced EMT, cell migration, and cell invasion, which are reversed by overexpression of MALAT1, demonstrating that MALAT1 and miR-141-5p may be important regulators in the initiation and metastasis of PC.