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Small cell lung cancer growth is inhibited by miR-342 and its target gene IA-2

Thursday, September 17, 2015 — Poster Session II

12:00 p.m. – 1:30 p.m.
FAES Terrace
NIDCR
CANCER-35

* FARE Award Winner

Authors

  • H Xu
  • T Cai
  • G Carmona
  • L Abuhatzira
  • AL Notkins

Abstract

Background: Small cell lung cancers (SCLC) are neuroendocrine tumors. Earlier studies from our laboratory showed that SCLC expresses high levels of IA-2 as compared to normal lung cells. The secretion of hormones from these cells is thought to have an autocrine effect on lung tumor growth. IA-2 is known to be involved in the secretion of hormones and neurotransmitters. Recently, we showed that one of the targets of microRNA-342 was IA-2 and that miR-342 mimics suppressed the expression of IA-2. Aims: To determine the effect of knocking down the level of IA-2 by RNAi or by overexpression of miR-342 on lung tumor growth. Results: Knockdown of IA-2 by RNAi reduced tumor growth within four days by 40% or more. Similar results were obtained when these cell lines were transfected with miR-342 mimic. The knockdown of IA-2 by RNAi or the miR-342 mimic also resulted in a significant decrease in the secretion of acetylcholine (ACh), one of the autocrine hormones secreted by SCLC. Further studies revealed that the growth of SCLC cell lines that had been treated with the miR-342 mimic, was restored to nearly normal levels by treatment with acetylcholine. Conclusion: Our studies show for the first time that both miR-342 and its target gene IA-2 are involved in the growth of SCLC tumors and act by their effect on autocrine secretion. These findings point to possible new therapeutic approaches for the treatment of autocrine-induced tumor proliferation.

Category: Cancer Biology