LncRNA‐MALAT1 regulates proliferation and apoptosis of acute lymphoblastic leukemia cells via miR‐205‐PTK7 pathway

Abstract

Long non-coding RNA (lncRNA) MALAT1 has been confirmed to function as an oncogene in various solid tumors. MALAT1 level has been shown to be upregulated in relapsed acute lymphoblastic leukemia (ALL) patients, but the mechanism is unclear. This study aims to investigate the functional roles and underlying mechanisms of MALAT1 in ALL. MALAT1 and miR-205 expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). MTT assay and flow cytometry were performed to evaluate cell proliferation and apoptosis, respectively. Protein level of protein tyrosine kinase-7 (PTK7) was detected by Western blot assay. Dual luciferase reporter assay was conducted to confirm the binding of MALAT1 and miR-205, as well as miR-205 and PTK7. The levels of MALAT1 and PTK7 were upregulated in ALL samples. In contrast, miR-205 level was downregulated in ALL in ALL samples. Moreover, MALAT1 silencing or miR-205 overexpression restrained proliferation and promoted apoptosis of ALL cells. Mechanistically, MALAT1 sponged miR-205 to regulate PTK7 expression. In summary, MALAT1 affected ALL cell proliferation and apoptosis via regulating miR-205-PTK7 axis. Our results suggest that MALAT1-miR-205-PTK7 axis participates in the proliferation and apoptosis of ALL, which may provide a potential treatment target for ALL.

IGF2BP2 Regulates MALAT1 by Serving as an N6-Methyladenosine Reader to Promote NSCLC Proliferation

“…However, MALAT1 serves as an oncogenic lncRNA in NSCLC proliferation and Gefitinib resistance by acting as a miR-200a sponge ( Feng et al, 2019 ). Consistently, lncRNA MALAT1 also plays a pro-oncogenic role in ovarian cancer ( Jin et al, 2017 ), osteosarcoma ( Zhang et al, 2020 ), acute lymphoblastic leukemia ( Song Y. et al, 2020 ), and colorectal cancer ( Guo et al, 2020 ). Our results showed that IGF2BP2 overexpression increased the MALAT1 level, whereas MALAT1 was significantly downregulated by IGF2BP2 knockdown, suggesting that lncRNA MALAT1 can be regulated by IGF2BP2.…”

Targeting the lncRNA DUXAP8/miR-29a/PIK3CA Network Restores Doxorubicin Chemosensitivity via PI3K-AKT-mTOR Signaling and Synergizes With Inotuzumab Ozogamicin in Chemotherapy-Resistant B-Cell Acute Lymphoblastic Leukemia

“…Since the concept of lncRNA is just initiated in a short time, in-depth studies of its mechanisms underlying ALL are very limited, and only a few studies have reported several specific lncRNAs that are involved in ALL pathogenesis, such as lncRNA MALAT1, lncRNA VPS9D1-AS1, and lncRNA TEX41 ( 18 , 30 , 31 ). However, few studies on lncRNA have been disclosed in the context of B-ALL chemotherapy resistance.…”

Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases

“…In this study, MALAT1, a long non-coding RNA (lncRNA) was identified as a regulator of ALL cell proliferation by regulating miR-205. This last has a target in PTK7, a protein tyrosine-kinase [ 116 ]. miR-152 is also regulated by a lncRNA (LINC00221) and presents a role in ALL cell proliferation and apoptosis [ 117 ].…”