piRNAs as Biomarkers for Cancer

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piRNAs as Biomarkers for Cancer

Piwi-interacting RNAs (piRNAs) are a class of small RNAs that are about 24-32 nucleotides long. They have a strong uracil bias at the 5' end and 2'-O-methylation at the 3' end. The latest evidence suggests that piRNAs mainly exist in the stem and germ cells of fruit flies, mice, human beings, and other mammals. piRNA forms the piRNA complex by combining with the PIWI protein, which recognizes and binds transposons, cleaved mRNA produced by transposon gene transcription or silenced transposon genes in the cell nucleus, so as to regulate the self-renewal of germ cells and proliferation and differentiation of stem cells. In addition to mammalian germ lines, piRNAs are expressed in various human tissues in tissue-specific ways. Besides, piRNA regulates key signaling pathways at the transcriptional or post-transcriptional level.

piRNAs have a series of regulatory functions. Figure 1. piRNAs have a series of regulatory functions. (Li M, et al. 2020)

The Role of piRNAs in Cancer

In recent years, through the researches on the role of piRNA and PIWI in cancer, scientists have found some evidence supporting the close links between piRNA/PIWI and various tumors. Busch, et al. found that different types of piRNA expression were significantly correlated with tumor cell metastasis, which could result in dysregulation of signaling pathways in tumor cells. Abnormal expression of PIWI proteins is related to tumor formation. The expression level of the PIWI protein in breast cancer and lung cancer was significantly higher than that in normal cells. The PIWI protein inhibits tumor cell apoptosis and promotes tumor proliferation through acting on the STAT3/bcl-xl and STAT3/Cyclin D1 signaling pathways. PIWIL2 is a member of the PIWI family; overexpression of PIWIL2 silences tumor-suppressor transposons and promotes tumor development. PIWIL4, a member of the PIWI subgroup, was initially found in animal testicular tissue. PIWIL4 interacts with piRNA and is commonly expressed in various human tissues, including the ovary. The PIWIL4 gene is highly expressed in cholangiocarcinoma tissues, and its up-regulated expression plays a crucial role in the occurrence, development, and prognosis of cholangiocarcinoma.

piRNAs as Cancer Biomarkers

The abnormal expression of piRNA is related to a variety of cancers and may play a pro-cancer or anti-cancer role in cancer initiation, progression, and metastasis. The potential clinical significance of piRNA and PIWI as diagnostic tools, therapeutic targets, and prognosis biomarkers in cancer was highlighted. Due to the possible role of piRNAs in various carcinogenesis processes, there are new promising opportunities in this field. Among them, an exciting possibility consists in the application of piRNA investigations to provide early diagnosis, and even prevent the development of cancer. This hypothesis is supported by preliminary analyses of piRNA profiles in samples adjacent to tumor tissue, which shows a profile of expressed piRNAs that is more similar to cancer tissue pattern of expression than normal mucosa. Therefore, piRNAs might be considered as possible biomarkers of the cancer field effect.

Table 1. The function of the abnormal expression of piRNA and PIWIL in different cancer cells. (Guo B, et al. 2020)

CancerMoleculesExpressionFunction
Gastric cancerpiR-651Diagnostic tool or therapeutic target
piR-823Diagnostic tool or therapeutic target
PIWIL1Prognosis biomarker
Breast cancerpiR-651Diagnostic tool
piR-4987Prognosis biomarker
piR-36,712Prognosis biomarker or therapeutic target
piR-021285Prognosis biomarker
piR-932Therapeutic target
PIWIL1Diagnostic tool
PIWIL2Therapeutic target
Renal cancerpiR-32051Prognosis biomarker
piR-39894Prognosis biomarker
piR-43607Prognosis biomarker
piR-30924Prognosis biomarker
piR-38756Prognosis biomarker
piR-57125Prognosis biomarker
piR-34536Prognosis biomarker
piR-51810Prognosis biomarker
PIWIL1Prognosis biomarker
PIWIL2Prognosis biomarker
PIWIL4Prognosis biomarker
piR-823Diagnostic tool
Colorectal cancerpiR-54265Therapeutic target
piR-823Therapeutic target
piR-18849Prognosis biomarker
piR-19521Prognosis biomarker
piR-1245Prognosis biomarker
PIWIL1Prognosis biomarker
piR-5937Diagnostic tool
piR-28876Diagnostic tool
Lung cancerpiR-55490Prognosis biomarker
piR-651Diagnostic tool
PIWIL1Prognosis biomarker

References:

  1. Xu J, et al. Biological significance of piRNA in liver cancer: a review. Biomarkers, 2020, 25(6): 436-440.
  2. Guo B, et al. piRNAs: biogenesis and their potential roles in cancer. Cancer and Metastasis Reviews, 2020: 1-9.
  3. Li M, et al. Piwi-interacting RNAs (piRNAs) as potential biomarkers and therapeutic targets for cardiovascular diseases. Angiogenesis, 2020: 1-16.
  4. Lin Y, et al. PIWI-interacting RNAs in human cancer. Seminars in Cancer Biology. Academic Press, 2020.
  5. Assumpção C B, et al. The role of piRNA and its potential clinical implications in cancer. Epigenomics, 2015, 7(6): 975-984.
  6. Chalbatani G M, et al. Biological function and molecular mechanism of piRNA in cancer. Practical laboratory medicine, 2019, 13: e00113.

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