# miR-200 miRNAs repress tumor metastasis in lung adenocarcinoma

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $278,388

## Abstract

Project summary
Lung cancer is the leading cause of cancer death worldwide, largely due to its highly metastatic
nature. Hence, elucidating the molecular mechanisms for tumor metastasis remains one of the
most pressing challenges in lung cancer research. To date, most studies on cancer metastasis
have focused on protein-coding genes, yet it has become increasingly clear that non-coding
RNAs, particularly, microRNAs (miRNAs), are integral components of the molecular network for
cancer metastasis, Using a Kras-driven, p53 deficient lung adenocarcinoma mouse model, we
compared the miRNA expression profiles between primary and metastatic lung tumors, and
identified miR-200 miRNAs as the most downregulated miRNAs in lung cancer metastases. The
miR-200 family consists of five homologous miRNAs located at two genomic loci: mir-
200b/200a/429 and mir-200c/141. To characterize miR-200 functions in lung cancer metastasis,
we generated KrasLSL-G12D/+;p53fl/fl; mir-200c/141-/- (KP200cKO) mice, which exhibited a significant
increase of tumor metastases within a short latency. Interestingly, all metastatic KP200cKO
tumors examined exhibited a complete silencing of all miR-200 miRNAs, suggesting that a
complete loss of miR-200 redundancy was essential for developing cancer metastasis in this
model. Based on these preliminary findings, we hypothesize that miR-200 miRNAs are key
repressors of cancer metastasis in Kras-driven, p53 deficient lung adenocarcinomas. Using
mouse genetics, CRISPR genome editing, cell and molecular approaches, we propose to
comprehensively characterize the importance of miR-200 miRNAs during lung cancer
metastasis, and will elucidate the underlying molecular and cellular mechanisms that govern the
biological functions and transcriptional regulation of miR-200 miRNAs. Our proposed studies will
provide important insights into a highly robust mechanism to repress lung cancer metastasis.

## Key facts

- **NIH application ID:** 9984861
- **Project number:** 5R01CA139067-09
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Lin He
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $278,388
- **Award type:** 5
- **Project period:** 2009-08-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984861

## Citation

> US National Institutes of Health, RePORTER application 9984861, miR-200 miRNAs repress tumor metastasis in lung adenocarcinoma (5R01CA139067-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984861. Licensed CC0.

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