Long noncoding RNA MALAT1 regulates HDAC4‐mediated proliferation and apoptosis via decoying of miR‐140‐5p in osteosarcoma cells

Abstract

Noncoding RNAs regulate the initiation and progression of osteosarcoma (OS). The role of long noncoding RNA metastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) playing in OS and whether the function it working out was achieved through HDAC4 pathway remain uncovered. In this study, we illustrated that MALAT1 was upregulated and was correlated with poor prognosis in OS patients. Meanwhile, we demonstrated that a depression of MALAT1 suppressed proliferation and promoted apoptosis in OS cell line HOS and 143B. Further, we verified that MALAT1 exerting its function via upregulating of histone deacetylase 4 (HDAC4). Through an online prediction, a series of luciferase assays and RNA pull‐down assays, we demonstrated that both MALAT1 and HDAC4 were the targets of microRNA‐140‐5p (miR‐140‐5p) via sharing a similar microRNA responding elements. Even further, we revealed that MALAT1 served as a ceRNA of HDAC4 via decoying of miR‐140‐5p. Finally, we proved that MALAT1 promoted OS tumor growth in an in vivo animal study. In summary, the outcomes of this study demonstrated the complex ceRNA network among MALAT, miR‐140‐5p, and HDAC4‐mediated proliferation and apoptosis in OS. This study might provide a new axial in molecular treatment of OS.

LncRNA MALAT1 protects cardiomyocytes from isoproterenol‐induced apoptosis through sponging miR‐558 to enhance ULK1‐mediated protective autophagy

“…Especially for MALAT1, it was reported that MALAT1, as an important lncRNA in cancer, has been shown to promote the metastasis, proliferation, and invasion through various mechanisms (X. Zhang, Hamblin, & Yin, ). For example, MALAT1 could regulate the proliferation and apoptosis of osteosarcoma cells via decoying miR‐140‐5p (Sun & Qin, ). MALAT1 has been shown to promote the migration and invasion of lung cancer cells through targeting miR‐206 and Akt/mechanistic target of rapamycin (mTOR) signaling (Tang, Xiao, Chen, & Deng, ).…”

Long Noncoding RNAs in Osteosarcoma: Mechanisms and Potential Clinical Implications

“…Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) lncRNA affects the apoptotic osteosarcoma cell machinery through the RhoA/ROCK signal transduction pathway [88]. MALAT1also regulates osteosarcoma cell proliferation and apoptosis through upregulation of histone deacetylase 4 (HDAC4) by decoying miR-140-5p [199].…”

Long non-coding RNA PGM5-AS1 modulates epithelial-mesenchymal transition and invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition

“…The double DIG-labeled LNA microRNA probe (QIAGEN, Shanghai, China) for miR-140-5p was incubated with the paraffin-embedded osteosarcoma tissue sections. Briefly, after being deparaffinized, the tissue sections were treated with proteinase K (Roche, Basel, Switzerland), hybridized with 300 ng/mL probe at 60℃ for 16 h, then incubated with anti-digoxygenin-AP (AP-conjugated Fab fragments) (11093274910, Roche, Basel, Switzerland) at 25℃ for1 h, and lastly added with BM Purple (11442074001, Roche, Basel, Switzerland) for color reaction [16][17][18]. Osteosarcoma cells were plated into a 6-well plate with 3 × 10 5 cells in each well.…”