High Expression of Long Noncoding RNA HOTAIRM1 is Associated with the Proliferation and Migration in Pancreatic Ductal Adenocarcinoma
- 57 Downloads
Pancreatic ductal adenocarcinoma (PDAC) is an incurable malignancy. Long noncoding RNA (LncRNA) HOTAIRM1 (HOX antisense intergenic RNA myeloid 1) has been shown to play important roles in the progression of several type cancers. However, the exact role of HOTAIRM1 in PDAC development remains largely unknown. This study aims to evaluate the potential function of HOTAIRM1 in the development and progress of PDAC. HOTAIRM1 expression was measured by RT-qPCR in forty seven paired human PDAC tissues and five PDAC cell lines. SW1990 and PANC-1 cells were transfected with siHOTAIRM1 to achieve HOTAIRM1 silence. MTT assay and colony formation assay were used to detect the effect of HOTAIRM1 knockdown on cell proliferation. The impact of HOTAIRM1 silence on cell cycle and apoptosis was assessed by flow cytometry assay. Transwell migration assay was performed to explore the influence of HOTAIRM1 downregulation on the migratory potential of PDAC cells. Western blot assay was applied to determine the expression changes of cell cycle, apoptosis, and migration-related genes before and after downregulating HOTAIRM1. HOTAIRM1 expression was abnormally upregulated in PDAC tissues and cells when compared with the control samples, and was positively associated with the expression of KRAS gene mutation. In vitro functional experiments, HOTAIRM1 expression was significantly downregulated by transfection with siHOTAIRM1 in SW1990 and PANC cell lines. HOTAIRM1 knockdown attenuated cell proliferation by inducing cell cycle arrest at G0/G1 phase, promoted cell apoptosis, and inhibited cell migration in PDAC cells by regulating related-genes expression. In conclusion, HOTAIRM1 plays a critical role in PDAC progression, which may be a novel diagnostic and rational therapeutic target for the treatment of pancreatic ductal adenocarcinoma.
KeywordsHOTAIRM1 Pancreatic ductal adenocarcinoma Proliferation Migration
This study was supported by National Natural Science Foundation of China (Grant No.: 81460152) and Ningxia Medical University Scientific Research Project (Grant No.: XY201823).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 2.Taher MA, Khan ZR, Chowdhury MM, Nureelahi M, Chowdhury AK, Faruque MS, Wahiduzzaman M, Haque MA (2015) Pylorus preserving pancreaticoduodenectomy vs. standard Whipple's procedure in case of carcinoma head of the pancreas and periampullary carcinoma. Mymensingh Med J 24:319–325Google Scholar
- 14.Ding YC, Yu W, Ma C, Wang Q, Huang CS, Huang T (2014) Expression of long non-coding RNA LOC285194 and its prognostic significance in human pancreatic ductal adenocarcinoma. Int J Clin Exp Pathol 7:8065–8070Google Scholar
- 20.Marina DB, Salut B, Josep N, Marta P, Anna C, David G, Lourdes E, Mar T, Inmaculada H, Maria RJ (2015) The lincRNAHOTAIRM1, located in theHOXAgenomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature. Oncotarget 6:31613Google Scholar
- 21.Chen Y, Wu JJ, Lin XB, Bao Y, Chen ZH, Zhang CR, Cai Z, Zhou JY, Ding MH, Differential WXJ (2015) lncRNA expression profiles in recurrent gliomas compared with primary gliomas identified by microarray analysis. Int J Clin Exp Med 8:5033–5043Google Scholar
- 24.Yi Z, Shi M, Hao C, Gu J, Zhang J, Shen B, Deng X, Xie J, Xi Z, Peng C (2015) NPM1 activates metabolic changes by inhibiting FBP1 while promoting the tumorigenicity of pancreatic cancer cells. Oncotarget 6:21443–21451Google Scholar
- 28.Su X, Malouf GG, Chen Y, Zhang J, Yao H, Valero V, Weinstein JN, Spano JP, Meric-Bernstam F, Khayat D (2014) Comprehensive analysis of long non-coding RNAs in human breast cancer clinical subtypes. Oncotarget 5:9864–9876Google Scholar
- 29.Hezel AF, Kimmelman AC, Stanger BZ, Bardeesy N, Depinho RA (2015) Genetics and biology of pancreatic ductal adenocarcinoma. Genes Dev 29:595–608Google Scholar
- 32.Ijichi H, Chytil A, Gorska AE, Aakre ME, Fujitani Y, Fujitani S, Wright CVE, Moses HL (2006) Aggressive pancreatic ductal adenocarcinoma in mice caused by pancreas-specific blockade of transforming growth factor-β signaling in cooperation with active Kras expression. Genes Dev 20:3147–3160CrossRefGoogle Scholar
- 37.Zhi X, Chen W, Xue F, Liang C, Chen BW, Zhou Y, Wen L, Hu L, Shen J, Bai X (2015) OSI-027 inhibits pancreatic ductal adenocarcinoma cell proliferation and enhances the therapeutic effect of gemcitabine bothin vitroandin vivo. Oncotarget 6:26230–26241Google Scholar