Molecular mechanism of prostate cancer subtype unravelled

• The molecular mechanism and pathobiology of SPINK1-positive prostate cancer subtype, the second most recurrent and aggressive in nature, that affects about 15% of patients has been finally unravelled.

• The study was done by a multi-institutional team led by Prof. Bushra Ateeq from the Department of Biological Sciences and Bioengineering at Indian Institute of Technology (IIT) Kanpur.

About SPINK1

• The SPINK1-positive prostate cancer subtype derives its name from the excess amount of SPINK1 oncogene found in the cancer cells.

• Excess production of SPINK1 gene responsible for tumour and metastasis is not restricted to prostate cancer alone but also seen in colorectal, lung, pancreatic, breast and ovarian cancers.

• The insights gained in this study might therefore help in the treatment and disease management of several SPINK1-positive malignancies.

• In addition to excess amount of the SPINK1 oncogene, the researchers found that most cancer cells belonging to this subtype also have more than normal amount of a particular protein called EZH2.

• Also, the levels of two microRNAs (miRNA-338-5p and miRNA-421) produced in SPINK1-positive cancer cells were much less.

Findings corroborated

• The researchers first discovered excess levels of SPINK1 protein and reduced amount of the two microRNAs on analysing the global data sets of prostate cancer patients.

• These findings were then corroborated in SPINK1-positive prostate cancer cell lines.

• To validate the role of the two microRNAs in regulating the expression of the SPINK1 oncogene, the researchers introduced the microRNAs into the SPINK1-positive cancer cell lines.

• When the amount of microRNAs in the cell lines was increased, the SPINK1 level reduced and there were marked changes in the oncogenic properties — the cell proliferation and invasion reduced.

• Metastasis was also significantly reduced in both the lungs and bone marrow of mice implanted with microRNA-modified prostate cancer cells. But metastasis results were a little different in the case of chicken.

• While metastasis was less in the lungs, but both control and microRNA modified cancer cells failed to metastasise in the liver.

• The researchers tested the effectiveness of epigenetic drugs to restore the levels of the microRNAs and reduce the expression of the SPINK1 gene using SPINK1-positive cancer cell lines that did not have the two microRNAs.

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Mains Paper 3: Science & Technology

Prelims level: SPINK1

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