Breast Cancer

Breast Cancer

Breast cancer is a heterogeneous disease characterized by high genomic instability. Copy number variations, somatic mutations and chromosomal rearrangements are some of the frequently seen genetic alterations. Breast cancer is classified into 4 major subtypes: Luminal A, Luminal B, Triple negative, HER2 enriched [1][2]. It is determined by the tumor stage, tumor grade, status of the hormone receptors (PR, ER) and the mutation status of HER2.

Genes in breast cancer:
ATM BRCA1 BRCA2 CDH1 CHEK2 ER HER2 p53 PALB2 PTEN PR STK11 MUC1

Genes that convey moderate risk:
BARD1 BRIP1 CASP8 CTLA4 CYP19A1 FGFR2 H19 LSP1 MAP3K1 MRE11A MSH6 NBN RAD51D TM TERT


MicroRNA in Breast Cancer [3]

microRNAs are small non-coding RNA molecules that play a significant role in regulation of gene expression via RNA silencing and post-transcriptional regulation pathways. In breast cancer, differential expression of miRNA plays a critical role in regulating the invasion process by influencing cytoskeletal structure, cell-cell adhesion junctions, cancer cell-ECM interaction, tumor microenvironment, EMT transition and cancer stem cell abilities. Understanding miRNA’s role in breast cancer will enable a better management of breast cancer metastasis.

Human miRNAs in breast cancer

Up regulated:
hsa-miR-21b hsa-miR-29b hsa-miR-155
Down regulated:
hsa-miR-10b hsa-miR-125 hsa-miR-14

Refer to the table below for a list of all microRNAs involved in breast cancer

Name of miRNA miRNA expression pattern Target Genes affected by miRNA miRNA Role in Invasion-Metastasis Cascade
miR-142-3p UP ITGAV, WASL, RAC1, CFL2 Cancer cell invasiveness inhibition
miR-495 UP JAM-A Cancer cell migration
miR-10b UP HOXD10 Cell migration and invasion
miR-373 UP ITGA2 Cell migration, metastasis
miR-103/107 UP DICER1 EMT, cell migration, metastasis
miR-661 UP NECTIN1, STARD10 EMT, invasion
miR-221/222 UP TRPS1 EMT, invasion and migration (basal-like BC)
miR-23a UP CDH1 EMT, metastasis
miR-374a UP WIF1, PTEN, WNT5A EMT, metastasis
miR-22 UP TET1-3 EMT, stemness
miR-155 UP RHOA EMT, tight junction dissolution, migration and invasion
miR-191/425 UP DICER1 Invasion and metastasis
miR-221 UP CDH1 Invasion and metastasis
miR-221 UP DNMT3B Pluripotency and stemness
miR-21 UP TPM1 Tumor growth and malignant phenotype
miR-145 DOWN JAM-A Cancer cell motility inhibition
miR-145 DOWN JAM-A Cancer cell motility inhibition
miR-198 DOWN CDCP1 Cell adhesion and migration inhibition
miR-154 DOWN ADAM9 Cell migration and invasion inhibition
miR-200a DOWN CX43 Cell migration and metastasis inhibition
miR-206 DOWN CX43 Cell migration and metastasis inhibition
miR-181a-5p DOWN MMP14 Cell migration inhibition
miR-539 DOWN LAMA4 Cell migration inhibition (TNBC)
miR-7 DOWN PAK1 Cell motility and invasiveness inhibition
miR-494 DOWN PAK1 Clonogenic ability and cell migration, invasion and metastasis inhibition
miR-29b DOWN VEGFA, ANGPTL4, PDGF, LOX, MMP9 EMC re-modeling and metastasis inhibition
miR-200c DOWN ZEB1, TKS5, MYLK EMT and invadopodia forming inhibition
miR-153 DOWN MTDH EMT and invasion inhibition
miR-124 DOWN SNAI2 EMT and metastasis inhibition
miR-200b DOWN FERMT2 EMT and metastasis inhibition
miR-34 DOWN SNAI1 EMT inhibition
miR-205 DOWN ZEB1, ZEB2 EMT inhibition
miR-375 DOWN SHOX2 EMT inhibition
miR-506 DOWN SNAI2, VIM, CD151 EMT, adhesion, invasion, and migration inhibition
miR-30a DOWN ZEB2 EMT, invasion and distal spreading inhibition (TNBC)
miR-203 DOWN SNAI1 EMT, invasion and metastasis inhibition
miR-34c DOWN NOTCH4 EMT, migration and self-renewal inhibition
miR-320 DOWN ETS2 Inhibition of tumor micro-environment re-programming
miR-200 cluster DOWN WAVE3 Invasion and cell migration inhibition
miR-33a DOWN ADAM9 Invasion and metastasis inhibition
miR-193b DOWN uPA Invasion and metastasis inhibition
miR-335 DOWN TNC, SOX4 Invasion and metastasis inhibition
miR-720 DOWN TWIST1 Invasion and metastasis inhibition
miR-126 DOWN ADAM9 Invasion inhibition
miR-181a DOWN uPA Invasion inhibition
miR-193a/b DOWN uPA Invasion inhibition
miR-221/222 DOWN ITGB4, STAT5A, ADAM17 Invasion inhibition (luminal BC)
miR-224 DOWN CDC42, CXCR4 Invasion, metastasis inhibition
miR-31 DOWN WAVE3 Invasive phenotype reduction
miR-126 DOWN CXCL12 Metastasis inhibition
miR-124a DOWN Proliferation and metastasis inhibition
miR-708 DOWN LSD1 Proliferation, invasion inhibition
miR-30 DOWN UBC9 Self-renewal
let-7 DOWN H-RAS, HMGA2 Self-renewal, stemness
miR-590 DOWN SOX2 Stemness
miR-140 DOWN SOX2 Stemness, self-renewal
miR-183 cluster DOWN BMI1 Stemness, self-renewal

References:

  1. Associations between cancer predisposition testing panel genes and breast cancer, Couch et al, JAMA, 2017
  2. Identification of six key miRNAs associated with breast cancer through screening large-scale microarray data, Liang et al, Oncol Lett. 2018
  3. MicroRNAs contribute to breast cancer invasiveness, Fridichova et al., Cell, 2019