LncRNA MALAT1 potentiates autophagy­associated cisplatin resistance by regulating the microRNA­30b/autophagy­related gene 5 axis in gastric cancer.

Gastric cancer (GC) is the fourth most common type of cancer worldwide and chemoresistance is a major obstacle to successful GC treatment. In the present study, reverse transcription­quantitative polymerase chain reaction analysis was used to measure the expression of metastasis­associated lung adenocarcinoma transcript 1 (MALAT1) and microRNA (miR)­30b. Western blot analysis was conducted to detect the protein expression of autophagy­related gene 5 (ATG5), p62 and LC3 (LC3­I and LC3­II). Cell viability and half maximal inhibitory concentration were determined by the Cell Counting Kit­8 assay. The green fluorescent protein (GFP)­LC3­positive cell percentage was determined by the GFP­LC3 puncta experiment. Luciferase reporter and RNA immunoprecipitation assays were used to explore the molecular associations among MALAT1, miR­30b and ATG5. MALAT1 was found to be highly expressed in CDDP­resistant AGS(AGS/CDDP) cells and CDDP­resistant HGC­27 (HGC­27/CDDP) cells. Cell viability was markedly increased in MALAT1­overexpressing AGS/CDDP cells, but was notably reduced in MALAT1­depleted HGC­27/CDDP cells. Moreover, MALAT1 potentiated CDDP resistance by facilitating autophagy in AGS/CDDP and HGC­27/CDDP cells. Further investigations demonstrated that MALAT1 inhibited miR­30b expression by direct interaction. Moreover, miR­30b abolished MALAT1­induced CDDP resistance by inhibiting autophagy in AGS/CDDP and HGC­27/CDDP cells. Furthermore, ATG5 was found to be a target of miR­30b. miR­30b weakened resistance to CDDP by inhibiting autophagy in AGS/CDDP and HGC­27/CDDP cells, while this effect was abrogated by increased ATG5 expression. Additionally, MALAT1 sequestered miR­30b from ATG5 to increase ATG5 expression in AGS/CDDP and HGC­27/CDDP cells. Therefore, MALAT1 potentiated autophagy­related CDDP resistance through suppressing the miR­30b/ATG5 axis in AGS/CDDP and HGC­27/CDDP cells, indicating that it may represent a promising target for the reversal of chemoresistance in GC.

miR-92a Inhibits Proliferation and Induces Apoptosis by Regulating Methylenetetrahydrofolate Dehydrogenase 2 (MTHFD2) Expression in Acute Myeloid Leukemia.

Aberrant expression of microRNA-92a (miR-92a) has been investigated in various cancers. However, the function and mechanism of miR-92a in acute myeloid leukemia (AML) remain to be elucidated. Our data showed that miR-92a was evidently downregulated and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) was remarkably upregulated in AML cell lines HL-60 and THP-1. Dual luciferase reporter assay revealed that MTHFD2 was a direct target of miR-92a. Gain- and loss-of-function analysis demonstrated that MTHFD2 knockdown or miR-92a overexpression notably inhibited proliferation and promoted apoptosis of AML cell lines. Restoration of MTHFD2 expression reversed proliferation inhibition and apoptosis induction of AML cells triggered by miR-92a. Moreover, an implanted tumor model in mice indicated that miR-92a overexpression dramatically decreased tumor growth and MTHFD2 expression in vivo. Taken together, our results suggest that miR-92a inhibits proliferation and induces apoptosis by directly regulating MTHFD2 expression in AML. miR-92a may act as a tumor suppressor in AML, providing a promising therapeutic target for AML patients.

Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer.

Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNA GAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.