BACKGROUND: We previously showed that miR-301a-3p affects the invasion and migration abilities of pancreatic cancer cells. Here, we explore the role of miR-301a-3p in chemoresistance, which represents a major obstacle in cancer treatment. METHODS: We tested the effects of miR-301a-3p ongemcitabine resistance in cytotoxicity assays in vitro and in vivo. We used quantitative real-time PCR (qRT-PCR) to measure miR-301a-3p expression in wild-type and gemcitabine-resistant pancreatic cancer cells. We performed Western blot, qRT-PCR, and luciferase and rescue assays to confirm the direct target of miR-301a-3p. RESULTS: The overexpression and inhibition of miR-301a-3p promoted and reversed, respectively, gemcitabine resistance in pancreatic cancer cells in vitro. The role of miR-301-3p in chemoresistance was dependent on PTEN. The suppression of miR-301-3p expression sensitized pancreatic cancer cells to gemcitabine chemotherapy in a xenograft mouse model. CONCLUSION: MiR-301a-3p confers resistance to gemcitabine by regulating the expression of PTEN. The co-delivery of miR-301a-3p and gemcitabine might be an effective therapeutic regimen for patients with pancreatic cancer.
BACKGROUND: We previously showed that miR-301a-3p affects the invasion and migration abilities of pancreatic cancer cells. Here, we explore the role of miR-301a-3p in chemoresistance, which represents a major obstacle in cancer treatment. METHODS: We tested the effects of miR-301a-3p ongemcitabine resistance in cytotoxicity assays in vitro and in vivo. We used quantitative real-time PCR (qRT-PCR) to measure miR-301a-3p expression in wild-type and gemcitabine-resistant pancreatic cancer cells. We performed Western blot, qRT-PCR, and luciferase and rescue assays to confirm the direct target of miR-301a-3p. RESULTS: The overexpression and inhibition of miR-301a-3p promoted and reversed, respectively, gemcitabine resistance in pancreatic cancer cells in vitro. The role of miR-301-3p in chemoresistance was dependent on PTEN. The suppression of miR-301-3p expression sensitized pancreatic cancer cells to gemcitabine chemotherapy in a xenograft mouse model. CONCLUSION: MiR-301a-3p confers resistance to gemcitabine by regulating the expression of PTEN. The co-delivery of miR-301a-3p and gemcitabine might be an effective therapeutic regimen for patients with pancreatic cancer.
Entities:
Keywords:
PTEN; chemoresistance; gemcitabine; miRNA; pancreatic cancer
Authors: Susanna Obad; Camila O dos Santos; Andreas Petri; Markus Heidenblad; Oliver Broom; Cristian Ruse; Cexiong Fu; Morten Lindow; Jan Stenvang; Ellen Marie Straarup; Henrik Frydenlund Hansen; Troels Koch; Darryl Pappin; Gregory J Hannon; Sakari Kauppinen Journal: Nat Genet Date: 2011-03-20 Impact factor: 38.330
Authors: Muhammad Imran Aslam; Maleene Patel; Baljit Singh; John Stuart Jameson; James Howard Pringle Journal: J Transl Med Date: 2012-06-20 Impact factor: 5.531
Authors: Marissa Williams; Michaela B Kirschner; Yuen Yee Cheng; Jacky Hanh; Jocelyn Weiss; Nancy Mugridge; Casey M Wright; Anthony Linton; Steven C Kao; J James B Edelman; Michael P Vallely; Brian C McCaughan; Wendy Cooper; Sonja Klebe; Ruby C Y Lin; Himanshu Brahmbhatt; Jennifer MacDiarmid; Nico van Zandwijk; Glen Reid Journal: Oncotarget Date: 2015-09-15
Authors: Stefano Volinia; George A Calin; Chang-Gong Liu; Stefan Ambs; Amelia Cimmino; Fabio Petrocca; Rosa Visone; Marilena Iorio; Claudia Roldo; Manuela Ferracin; Robyn L Prueitt; Nozumu Yanaihara; Giovanni Lanza; Aldo Scarpa; Andrea Vecchione; Massimo Negrini; Curtis C Harris; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2006-02-03 Impact factor: 11.205
Authors: E Krasniqi; A Sacconi; G Blandino; P Vici; D Marinelli; L Pizzuti; M Mazzotta; D Sergi; E Capomolla; S Donzelli; M Carosi; A Bagnato; T Gamucci; S Tomao; C Natoli; P Marchetti; A Grassadonia; N Tinari; M De Tursi; E Vizza; G Ciliberto; L Landi; F Cappuzzo; M Barba Journal: Biomark Res Date: 2021-07-13
Authors: Meijie Sang; Aiying Li; Xu Wang; Can Chen; Kun Liu; Lin Bai; Ming Wu; Fei Liu; Meixiang Sang Journal: Transl Cancer Res Date: 2020-03 Impact factor: 1.241