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MS Public Seminar: MUNAZZA SAMAR KHAN

When & Where

April 15
2:00 PM - 3:00 PM
UTHealth Houston, McGovern Medical School, MSB B.645 and via Microsoft Teams (View in Google Map)

Contact

Event Description

Role of miR-4732-3p in Breast Cancer Brain Metastasis and Brain Metastatic Tumor Microenvironment 

Munazza Samar Khan (Advisor: Hui-Wen Lo, PhD)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. miR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal state. Additionally, we observed that extracellular vesicles secreted from miR-4732-3p-overexpressing TNBC cells significantly activated astrocytes. To identify how miR-4732-3p may activate astrocytes and also BCBM cells, we conducted cytokine arrays to identify significantly dysregulated cytokines, and found that multiple cytokines including FLT3LG can be upregulated in miR-4732-3p-overexpressing astrocytes. We further showed that FLT3LG significantly activates astrocytes and promotes astrocyte proliferation.  In agreement with the cytokine array results, FLT3LG mRNA is upregulated in astrocytes overexpressing miR-4732-3p. Finally, using TargetScan and GeneCards, we identified multiple potential miR-4732-3p target genes that are transcriptional repressors of FLT3LG, suggesting their potential roles in activating FLT3LG expression. These results collectively demonstrate that breast cancer-derived miR-4732-3p may play a novel important role in BCBM by promoting metastatic properties of BCBM cells, and activating astrocytes in the brain-metastatic tumor microenvironment through FLT3LG secretion.

Advisory Committee:

  • Hui-Wen Lo, PhD, Chair
  • Yoshua Esquenazi, MD
  • Tae Jin Lee, PhD
  • Kai Sun, MD, PhD
  • Aria Vaishnavi, PhD

Join via Microsoft Teams (Please contact Ms. Munazza Khan for her Microsoft Teams meeting info.)

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Role of miR-4732-3p in Breast Cancer Brain Metastasis and Brain Metastatic Tumor Microenvironment 

Munazza Samar Khan (Advisor: Hui-Wen Lo, PhD)

In this study, we aimed to identify microRNAs (miRNAs) that may play important roles in breast cancer brain metastasis (BCBM). To this end, we conducted miRNA-sequencing of extracellular vesicles isolated from the serum samples of 6 BCBM patients and 8 Stage I/II/III breast cancer patients, and identified 49 circulating miRNAs that were upregulated in BCBM patients compared to Stage I/II/III breast cancer. Upon further analysis, we identified miR-4732-3p to be upregulated in brain-tropic triple-negative breast cancer (TNBC) cell lines, compared to parental lines. miR-4732-3p overexpression increased metastatic properties of TNBC cells, including proliferation, migration, invasion, and maintenance of a mesenchymal state. Additionally, we observed that extracellular vesicles secreted from miR-4732-3p-overexpressing TNBC cells significantly activated astrocytes. To identify how miR-4732-3p may activate astrocytes and also BCBM cells, we conducted cytokine arrays to identify significantly dysregulated cytokines, and found that multiple cytokines including FLT3LG can be upregulated in miR-4732-3p-overexpressing astrocytes. We further showed that FLT3LG significantly activates astrocytes and promotes astrocyte proliferation.  In agreement with the cytokine array results, FLT3LG mRNA is upregulated in astrocytes overexpressing miR-4732-3p. Finally, using TargetScan and GeneCards, we identified multiple potential miR-4732-3p target genes that are transcriptional repressors of FLT3LG, suggesting their potential roles in activating FLT3LG expression. These results collectively demonstrate that breast cancer-derived miR-4732-3p may play a novel important role in BCBM by promoting metastatic properties of BCBM cells, and activating astrocytes in the brain-metastatic tumor microenvironment through FLT3LG secretion.

Advisory Committee:

  • Hui-Wen Lo, PhD, Chair
  • Yoshua Esquenazi, MD
  • Tae Jin Lee, PhD
  • Kai Sun, MD, PhD
  • Aria Vaishnavi, PhD

Join via Microsoft Teams (Please contact Ms. Munazza Khan for her Microsoft Teams meeting info.)

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