5.MicroRNAs (miRNAs)

1. Definition & Core Features

• miRNAs = microRNAs
• Non-coding RNA molecules
• Single-stranded
• Approx. ~22 nucleotides long
• Regulate gene expression post-transcriptionally
• Act as negative regulators

Mechanisms of action

miRNAs inhibit gene expression by:

1. Translation repression

– ribosome cannot read mRNA efficiently

2. mRNA cleavage/degradation

– message is destroyed

Memory hook:

miRNAs = “micro managers” → either block the message or cut it.

2. Why miRNAs matter in Cancer

miRNAs regulate:

• cell growth
• differentiation
• survival

Dysregulation alters balance:

Two main cancer-driving mechanisms:

Mechanism A – Overactive miRNAs targeting tumor suppressor genes

• ↑ miRNA activity
• ↓ tumor suppressor gene expression
• Removes brakes on cell proliferation/survival

These cancer-promoting miRNAs are called:

• OncomiRs

Memory hook:

OncomiRs = “overactive silencers of the good guys.”

Mechanism B – Loss of miRNAs that normally inhibit oncogenes

• ↓ miRNAs that restrain oncogene mRNA
• ↑ oncogene protein levels
• Presses accelerator on cell survival/growth

Cancer analogy:

Loss of TS-miRNAs = no guards → oncogenes run free.

3. Key Gene Examples Regulated by miRNAs in Cancer

Example 1 – BCL2

• Anti-apoptotic protein
• Loss/deletion of some miRNAs in:
• leukemias
• lymphomas
• → ↑ BCL2 levels
• Consequence: ↓ apoptosis → prolonged cancer cell survival

Example 2 – RAS

• Oncogene promoting proliferation
• miRNA dysregulation contributes in:
• lung tumors

Example 3 – MYC

• Proliferative oncogene
• miRNA dysregulation in:
• B-cell leukemias

Memory hook:

"RAS, MYC, BCL2 dance to the tune of miRNAs."

4. Flow Summary: miRNAs → Cancer

1. miRNAs are ~22 nt RNAs that regulate gene expression post-transcriptionally

via:

1. translation repression
2. mRNA cleavage
2. Pathway 1 – OncomiRs
• ↑ miRNAs targeting tumor suppressors
• ↓ tumor suppressor proteins
• → cancer development
3. Pathway 2 – Loss of tumor-suppressor miRNAs
• ↓ miRNAs targeting oncogenes
• ↑ oncogene proteins
• → cancer development
4. Example consequences:
• ↑ BCL2 in leukemias/lymphomas
• Dysregulation of RAS in lung tumors
• Dysregulation of MYC in B-cell leukemias

5. Summary Table – Compare Mechanisms

6. Final Take-Home

• miRNAs = small but powerful gene expression regulators
• Balanced miRNA signalling maintains normal control.
• In cancer, the balance is flipped:
• too much silencing of tumor suppressors
• too little silencing of oncogenes
• Net result:
• subtle post-transcriptional regulation by tiny RNAs has a major tumor-promoting impact when dysregulated.

If you'd like, I can now:

✔ convert this into an active recall sheet

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