Up-regulation of KISS1 as a novel target of Let-7i in melanoma serves as a potential suppressor of migration and proliferation in vitro.
Alkafaji. Haider A HA; Raji. Ahmed A; Rahman. Heshu S HS; Zekiy. Angelina O AO; Adili. Ali A; Jalili. Mohammadmahdi M; Hojjatipour. Tahereh T; Cid-Arregui. Angel A; Shomali. Navid N; Tarzi. Saeed S; Tamjidifar. Rozita R; Heshmati. Ramin R; Marofi. Faroogh F; Akbari. Morteza M; Hasanzadeh. Ali A; Deljavanghodrati. Mina M; Jarahian. Mostafa M; Sandoghchian Shotorbani. Siamak S
Key Findings
- Both Let-7i microRNA and KISS1 are lower in melanoma patients compared to healthy tissue.
- Increasing Let-7i in melanoma cells raises KISS1 expression, leading to reduced cell migration, proliferation, and increased apoptosis.
- Silencing KISS1 reverses the anti‑cancer effects of Let-7i, indicating that KISS1 mediates Let-7i’s protective role.
Practical Outcomes
- For now, the findings are purely laboratory‑based and do not translate into any safe, usable protocol for individuals. They suggest that future drug development might target Let-7i or kisspeptin pathways for melanoma treatment, but there is no actionable advice for self‑experimentation or longevity enhancement.
Summary
The study found that a tiny RNA molecule called Let-7i can boost the levels of a gene called KISS1, which makes kisspeptin proteins that help stop skin cancer cells from moving and growing. In lab experiments, adding Let-7i reduced cancer cell spread and caused them to die, while blocking KISS1 had the opposite effect.
Abstract
Melanoma is a kind of skin cancer that is begun by the alteration of melanocytes. miRNAs are small non-coding RNA molecules that regulate a variety of biological processes. KISS1, the metastasis-suppressor gene, encodes kisspeptins which inhibits migration and proliferation of cancers. This study was aimed to determine the role of Let-7i and KISS1 in melanoma cell migration and proliferation. At first, the expression of Let-7i and KISS1 was determined in patients with melanoma. In the in vitro part of the study, Let-7i mimics were transfected and the impact of its restoration on target gene expression, proliferation, migration and apoptosis of SK-MEL-3 melanoma cell line was assessed by real-time PCR and Western blotting, MTT assay, wound-healing assay and flow cytometry, respectively. Besides, KISS1 inhibitor siRNA alone and along with Let-7i was transfected to determine their probable correlation. The results revealed that either Let-7i or KISS1 were down-regulated in patients with melanoma. The results obtained from the in vitro part of the study revealed that restoration of Let-7i reduced the expression of metastasis- and proliferation-related target genes. Moreover, it was revealed that up-regulation of Let-7i attenuated migration and proliferation capability of SK-MEL-3 cells. Besides, it was demonstrated that Let-7i restoration induced apoptosis in melanoma cells. More importantly, the KISS1 inhibitor caused a prominent cell migration and proliferation, attenuated by Let-7i re-expression. To sum up, the present study revealed the impressive role of Let-7i restoration along with its correlation with KISS1 on melanoma carcinogenicity which may be applicable in future in vivo studies.
Study Information
pubmed
2021
2021-06-06T00:00:00.000Z
10.1111/jcmm.16695
5
45