The LIN28/let-7 Pathway in Cancer

Area of Science:

• Oncology
• Molecular Biology
• Gene Regulation

Background:

• Reduced let-7 microRNA expression is a frequent event in cancer, correlating with poor patient outcomes.
• LIN28A and LIN28B, proto-oncogenes, downregulate let-7 microRNAs post-transcriptionally in various cancers.
• LIN28A recruits ZCCHC11 (TUTase) to polyuridylate pre-let-7, inhibiting its biogenesis and tumor suppressor activity.

Purpose of the Study:

• To review the role of the LIN28/let-7 pathway in cancer.
• To discuss the pathway's involvement in tumorigenesis, cancer stem cell biology, metabolomics, metastasis, and treatment resistance.
• To highlight emerging therapeutic strategies targeting the LIN28/let-7 axis.

Main Methods:

• Literature review of studies investigating the LIN28/let-7 pathway.
• Analysis of molecular mechanisms underlying let-7 downregulation by LIN28A and LIN28B.
• Examination of preclinical and clinical evidence regarding the pathway's function in cancer.

Main Results:

• LIN28A/LIN28B activation leads to decreased let-7 levels, resulting in the overexpression of oncogenic targets like MYC and RAS.
• Ectopic LIN28 expression in mouse models accelerates tumorigenesis through a let-7 dependent mechanism.
• The LIN28/let-7 pathway influences cancer stem cell properties, metabolism, metastasis, and resistance to radiation and chemotherapy.

Conclusions:

• The LIN28/let-7 pathway is a critical regulator in cancer development and progression.
• Dysregulation of this pathway contributes to various hallmarks of cancer.
• Targeting the LIN28/let-7 axis represents a promising therapeutic avenue for cancer treatment.