# Surgical Studies on the Role of MicroRNAs in Esophageal Cancer

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2021 · —

## Abstract

Background: Despite significant reductions in the morbidity and mortality associated with esophagectomy,
survival for patients with esophageal cancer remains dismal. In most patients, adjunctive therapies including
chemotherapy and radiation are beneficial. In fact, patients who achieve a complete pathologic response
(pCR) after treatment with chemotherapy and radiation followed by esophagectomy often experience greatly
improved survival. Unfortunately, the percentage of patients who currently achieve a pCR is low. Improving
survival for esophageal cancer patients following esophagectomy requires that we ascertain how to increase
the number of patients who achieve a pCR. In other malignancies, microRNAs (miRs) have been found to
serve as effective diagnostic, prognostic, and predictive biomarkers. In addition, based on their ability to
function as oncogenes or tumor suppressors, miR-based therapeutic approaches are currently being
investigated. The role of miRs in the pathogenesis and treatment of esophageal cancer has not been
thoroughly evaluated.
Objectives: The primary objective of this study is to identify new biomarkers and therapeutic targets based an
analysis of miR expression and function in esophageal cancer cells.
Preliminary Findings: Our preliminary studies indicate that a) miR-214-3p and miR-199a-5p are dramatically
downregulated in esophageal cancer cell lines compared to esophageal epithelial cells, b) this expression
pattern has been verified in initial human tumor samples, c) specific binding interactions have been identified
between miR-214-3p and miR-199a-5p with the oncogenic targets survivin and mitogen activated protein
kinase kinase kinase 11 (MAP3K11), respectively, d) ectopic expression of miR-214-3p and miR-199a-5p
results in a marked decrease in the levels of survivin and MAP3K11 in esophageal cancer cells, and e) ectopic
expression of miR-214-3p and miR-199a-5p results in important functional consequences; specifically,
increased sensitivity to chemotherapy-induced apoptosis and decreased proliferation, respectively. Based on
these exciting observations, we HYPOTHESIZE that downregulation of miR-214-3p and miR-199a-5p occurs
frequently in esophageal cancer cells and can be exploited for prognostic, predictive, and therapeutic
purposes.
Methods: To test this hypothesis, we propose 3 specific aims. (1) To characterize expression of miR-
214-3p and miR-199a-5p in human esophageal cancer specimens and correlate expression with clinical
outcomes. Pretreatment biopsies of both tumor and normal esophageal epithelium will be obtained from 50
patients for evaluation of miR-214-3p and miR-199a-5p expression and correlation with outcomes. (2) To
identify novel targets of miR-214-3p and miR-199a-5p that contribute to the development and progression of
esophageal cancer. We will utilize human esophageal cancer cell lines to identify new targets and functions of
miR-214-3p and miR-199a-5p in esophageal cancer cells. (3) To determin...

## Key facts

- **NIH application ID:** 10364596
- **Project number:** 5I01CX001434-05
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** James M Donahue
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364596

## Citation

> US National Institutes of Health, RePORTER application 10364596, Surgical Studies on the Role of MicroRNAs in Esophageal Cancer (5I01CX001434-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10364596. Licensed CC0.

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