MicroRNA-141-3p regulates cellular proliferation, migration, and invasion in esophageal cancer by targeting tuberous sclerosis complex 1

Pornima Phatak, Michael Noe, Kaushal Asrani, Ingrid E. Chesnick, Bruce D. Greenwald, James M. Donahue

Research output: Contribution to journalArticlepeer-review

Abstract

MicroRNA (miR)−141-3p, which functions as an oncogene in multiple malignancies, has been shown to be highly overexpressed in esophageal cancer cells in our previous work. miR-141-3p is predicted to bind the messenger RNA (mRNA) of tuberous sclerosis complex 1 (TSC1), a tumor suppressor, with high affinity. In this study, we investigated the expression and functional interaction between miR-141-3p and TSC1 in esophageal cancer cells. Experiments were conducted in four esophageal cancer lines and in tumor cells isolated from human esophageal cancer specimens by laser capture microdissection. miR-141-3p expression was measured by real time and droplet digital PCR. Biotinylated RNA pull-down and luciferase reporter assays were used to assess binding. miR-141-3p function was tested by assessing proliferation, migration, invasion, and induction of autophagy following its silencing. We found that miR-141-3p levels were increased in TE7, OE33, and TE10 esophageal cancer cells compared to FLO-1 cells, with similar heterogeneity observed in human esophageal cancer specimens. Silencing of miR-141-3p led to increased TSC1 protein expression in these cells and was associated with increased TSC1 translation. Binding studies reveal that miR-141-3p binds to each of the predicted binding sites in the 3′-untranslated region of TSC1 mRNA. Following miR-141-3p silencing, TE7, OE33, and TE10 cells exhibited decreased proliferation, migration, and invasion, as well as enhanced autophagy. Importantly, these phenotypic effects were replicated by overexpression of TSC1 alone in these cells. Our results indicate that miR-141-3p functions in an oncogenic capacity in a subset of esophageal cancer cells, in part by suppressing TSC1 expression.

Original languageEnglish (US)
Pages (from-to)125-137
Number of pages13
JournalMolecular Carcinogenesis
Volume60
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • esophageal cancer
  • miR-141-3p
  • tuberous sclerosis complex 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'MicroRNA-141-3p regulates cellular proliferation, migration, and invasion in esophageal cancer by targeting tuberous sclerosis complex 1'. Together they form a unique fingerprint.

Cite this