MicroRNA-1290 promotes asiatic acid‑induced apoptosis by decreasing BCL2 protein level in A549 non‑small cell lung carcinoma cells.

Asiatic acid, a triterpenoid derived from Centella asiatica, is a putative anticancer agent in several types of cancer cells. Investigations of its biological role in negative regulation of cell growth have focused on the extent of induction of apoptosis in a cell-type-specific manner. In this study, we identified an important regulator of asiatic acid-induced cell death, microRNA (miR)-1290, which sensitizes cells to asiatic acid-induced cytotoxicity and negatively regulates BCL2 expression. Asiatic acid significantly upregulated miR-1290, and asiatic acid-induced cell death was shown to be dependent on miR-1290 activity. Molecular assays demonstrated that BCL2 mRNA is a direct target of miR-1290-mediated RNA interference. The results of functional studies suggest that miR-1290 suppresses cell viability and cell cycle progression. These data provide insight into miR-1290-mediated cellular mechanisms in asiatic acid-treated A549 non-small cell lung carcinoma cells.

[1]  Richard W. Kriwacki,et al.  Many players in BCL-2 family affairs. , 2014, Trends in biochemical sciences.

[2]  H. Fox,et al.  The evolutionary young miR-1290 favors mitotic exit and differentiation of human neural progenitors through altering the cell cycle proteins , 2014, Cell Death and Disease.

[3]  Zhongqiu Lin,et al.  Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer , 2013, Virology Journal.

[4]  R. Hruban,et al.  MicroRNA Array Analysis Finds Elevated Serum miR-1290 Accurately Distinguishes Patients with Low-Stage Pancreatic Cancer from Healthy and Disease Controls , 2013, Clinical Cancer Research.

[5]  Yongliang Zhu,et al.  Up-regulation of microRNA-1290 impairs cytokinesis and affects the reprogramming of colon cancer cells. , 2013, Cancer letters.

[6]  S. An,et al.  Ginsenoside Rh2 mediates changes in the microRNA expression profile of human non-small cell lung cancer A549 cells. , 2013, Oncology reports.

[7]  Satoru Takahashi,et al.  miR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer. , 2013, Endocrine-related cancer.

[8]  Su-Jae Lee,et al.  Centella asiatica protects against UVB-induced HaCaT keratinocyte damage through microRNA expression changes. , 2012, International journal of molecular medicine.

[9]  S. An,et al.  Titrated extract of Centella asiatica provides a UVB protective effect by altering microRNA expression profiles in human dermal fibroblasts. , 2012, International journal of molecular medicine.

[10]  S. An,et al.  CYP1A1 is a target of miR-892a-mediated post-transcriptional repression. , 2012, International journal of oncology.

[11]  J. Grigull,et al.  miRNA profiling for clear cell renal cell carcinoma: biomarker discovery and identification of potential controls and consequences of miRNA dysregulation. , 2011, The Journal of urology.

[12]  Munish Kumar,et al.  Loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis , 2011, Proceedings of the National Academy of Sciences.

[13]  M. Wei,et al.  Micro‐RNA‐21 regulates TGF‐β‐induced myofibroblast differentiation by targeting PDCD4 in tumor‐stroma interaction , 2011, International journal of cancer.

[14]  F. Slack,et al.  OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma , 2010, Nature.

[15]  R. Lavker,et al.  MicroRNA-21 acts as an oncomir through multiple targets in human hepatocellular carcinoma. , 2010, Journal of hepatology.

[16]  Loyal A Goff,et al.  Differential regulation of microRNA stability. , 2010, RNA.

[17]  Y. Pilpel,et al.  p53-independent upregulation of miR-34a during oncogene-induced senescence represses MYC , 2010, Cell Death and Differentiation.

[18]  Jing Gao,et al.  Protective Effects of Asiatic Acid on Rotenone- or H2O2-Induced Injury in SH-SY5Y Cells , 2009, Neurochemical Research.

[19]  Y. Lou,et al.  Protective effects of asiatic acid against D-galactosamine/lipopolysaccharide-induced hepatotoxicity in hepatocytes and kupffer cells co-cultured system via redox-regulated leukotriene C4 synthase expression pathway. , 2009, European journal of pharmacology.

[20]  Alice Shapiro,et al.  MicroRNA-21 targets a network of key tumor-suppressive pathways in glioblastoma cells. , 2008, Cancer research.

[21]  L. Lim,et al.  A microRNA component of the p53 tumour suppressor network , 2007, Nature.

[22]  Kwang Dong Kim,et al.  Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells. , 2006, Cancer letters.

[23]  Chun-ching Lin,et al.  Asiatic Acid, a Triterpene, Induces Apoptosis and Cell Cycle Arrest through Activation of Extracellular Signal-Regulated Kinase and p38 Mitogen-Activated Protein Kinase Pathways in Human Breast Cancer Cells , 2005, Journal of Pharmacology and Experimental Therapeutics.

[24]  M. Byrom,et al.  Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis , 2005, Nucleic acids research.

[25]  K. Kataoka,et al.  Inhibitory effects of asiatic acid and CPT-11 on growth of HT-29 cells. , 2005, The journal of medical investigation : JMI.

[26]  P. Houghton,et al.  Plants used in Chinese and Indian traditional medicine for improvement of memory and cognitive function , 2003, Pharmacology Biochemistry and Behavior.

[27]  D. Nam,et al.  Asiatic acid, a triterpene, induces apoptosis through intracellular Ca2+ release and enhanced expression of p53 in HepG2 human hepatoma cells. , 2002, Cancer letters.

[28]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[29]  P. Sastry,et al.  Apoptosis and the Nervous System , 2000, Journal of neurochemistry.

[30]  S. Hilsenbeck,et al.  Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells. , 1998, International journal of oncology.

[31]  D. Green,et al.  The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis , 1997, Science.

[32]  Dean P. Jones,et al.  Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked , 1997, Science.

[33]  G. R. Murray,et al.  The comparative steady-state bioavailability of the active ingredients of madecassol , 1993, European Journal of Drug Metabolism and Pharmacokinetics.

[34]  B. Hausen,et al.  Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer , 1993, Contact dermatitis.

[35]  R. Nakano.  Apoptosis: gene-directed cell death. An overview. , 1997, Hormone research.