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Table 1 Summary of disease-related piRNAs/PIWI proteins

From: The disease-related biological functions of PIWI-interacting RNAs (piRNAs) and underlying molecular mechanisms

piRNAs/PIWI proteins

Clinical relevance

Disease/abnormality

Confirmed/putative molecular mechanisms

References

piR-DQ541777

N/A

Spine morphogenesis defects

Targets Cdk5rap1 and Mark1/2

[14]

Hiwi

Altered hiwi expression had poorer prognosis

Lung, pancreatic, gastrointestinal, liver, breast, colorectal, and ovarian cancer

Influences Stat3/Bcl-X and Stat3/cyclinD1 signaling

[26,27,28,29,30,31,32,33,34,35,36,37,38]

piR-651

Upregulated. Potential biomarkers

Gastric, hepatic, breast, stomach, cervical, lung cancer, etc.

–

[42]

piR-823

Downregulated

Gastric cancer

–

[43]

piR-DQ596670

piR-DQ598183

piR-DQ597341

piR-DQ598252

piR-DQ596311

piR-DQ598677

piR-DQ597960

piR-DQ570994

Misregulated in tumor tissue

Breast cancer

–

[45]

piR-20365

piR-4987

piR-20582

piR-20485

Misregulated in tumor tissue among which piR-4987 expression correlates with lymph node metastasis

Breast cancer

–

[46]

piR-932

Potential drug target for inhibiting metastasis

Breast cancer

Stimulates the methylation of Latexin promoter region

[47]

piR-009051

piR-021032

piR-015249

piR-020541

piR-017061

piR-004153

piR-017716

piR-019914

Misregulated in tumor tissue. Among the listed piRNAs, 4 and 6 piRNAs are linked with OS and RFS respectively, 2 piRNAs are linked with both OS and RFS

Breast cancer

306 non–redundant gene targets was predicted for six piRNAs, which are enriched for cell events such as transcription, cell signaling, cytoskeleton organization, etc.

[48]

piR-360269

Significantly expressed in breast cancer

Breast cancer cell line MCF7

Targets SERPINA1 and LRAT

[49]

139 piRNAs

Among 139 piRNAs, 103 were upregulated, 36 were downregulated, 6 were common for stages I & II, 3 were common for stage II & III, while no common piRNAs for stage I & III. Eight were differentially expressed in all three stages

TNBC

–

[50]

piR-0211285

Genetic variant of piR-021285 is linked with increased breast cancer risk

Breast cancer

Affects methylation at four genes: AATF, ARHGAP11A, PIP4K2B and THAP10

[51]

19 piRNAs

Misregualted in tumor tissue. Upregulation of the three piRNAs are linked with RCC metastasis, poor cancer-specific survival and late clinical stage

RCC

–

[52]

235 piRNAs

369 piRNAs

piR-30924

piR-57125 piR-38756

Upregulated

Downregulated

Three piRNAs below were linked with OS in both non-metastatic and metastatic RCC. piR-38,756 is an independent marker for recurrence and survival prognosis in non-metastatic RCC

RCC

–

[53]

piR-823

Downregulation of piR-823 in tumor biopsies, while upregulation of piR-823 in blood serum and urine. Higher piR-823 levels in serum are correlated with advance clinical stages of RCC

RCC

–

[54]

106 piRNAs

91 piRNAs

piR-60152

Upregulated

Downregulated

Downregulated

Bladder cancer

piR-60152 targets TNFSF4

[55]

piR-25447

piR-23992

piR-28876

piR-22842

piR-23317

piR-26131

piR-23210.1

piR-25447

piR-27729

piR-7193.1

piR-7193.2

piR-27729.1

piR-27730.1

Three piRNAs on the top were misregulated in tumor group.

Ten piRNAs at the bottom were misregulated in metastasis group.

CRC

–

[57]

piR-823

Upregulated

CRC

Influences HTRA, IGFBP5, HSP27, HSP60 and HSP70.

Influences the transcriptional activity but not the expression of HSF1 by binding directly to HSF1 and promote its phosphorylation at Ser326

[58]

piR-1245

Correlates with advanced disease, metastasis and poor prognosis

CRC

Targets ATF3, BTG1, DUSP1, FAS, NFKBIA, UPP1, SESN2, TP53INP1 and MDX1

[59]

piR-DQ596225

piR-DQ596306

piR-DQ596309

piR-DQ596354

Prognostic markers for the OS and RFS of lung adenocarcinoma and lung squamous cell carcinoma patients

Lung cancer

–

[60]

piR-55490

Prognostic marker

Lung cancer

Inhibits Akt/mTOR signaling through binding to mTOR mRNA at 3’UTR and promote its degradation

[61]

piR-52200

piR-34871

piR-46545

piR-35127

Misregulated in H1229:RASSF1C

Lung cancer cell line H1229 overexpressing RASSF1C

–

[62]

piR-L-138

Upregulated following cisplatin (CDDP)-based chemotherapy

LSCC

Binds directly to p60-MDM2 protein to influence cell apoptosis

[63]

piR-651

Upregulated in lung cancer cell lines

NSCLC cell line A549 and HCC827

–

[64]

125 piRNAs

Misregulated in HCC compared with cirrhotic tissues

HCC

Predicted RNA targets are involved in key signaling pathways such as hepatocarcinogenesis and HCC progression

[65]

piR-823

Misregulated and positively correlated with clinical stage

MM

Affects p16INK4A/ cyclin D1/CDK4/Rb pathway. Influences VEGF secretion and restores p16INK4A expression through changing DNA methylation status

[66]

61 piRNAs

Misregulated

HNSCC

–

[67]

87 piRNAs

Misregulated. 41 out of the 87 piRNAs correlate with HPV infection status. 5 piRNAs correlate with worse OS

HPV-positive HNSCC

–

[68]

30 piRNAs

Misregulated

HPV16 (+) HNSCC

Targets PIWIL4 and RTL family of retrotransposon like genes

[69]

13 piRNAs

2 piRNAs are linked with tumor stage while 1 piRNA (NONHSAT067200) is a potential indicator of patient survival rate

HNSCC patients with smoking hostory

–

[70]

10 piRNAs

2 piRNAs are downregulated and 8 piRNAs are upregulated

Endometrium cancer

1526 putative mRNA targets were predicted among which 170 were aberrantly expressed in endometrium cancer tissue. The protein encoded takes parts in cell death, growth and survival

[72]

piR-598

harbor glioma-associated germline variants

glioma

–

[73]

piR-593,109

Upregulated

GEC

Affects MEG3/miR-330-5p/RUNX3 signaling

[74]

525 piRNAs

Common in two NB cell lines

NB

589 putative target mRNAs were found. Protein encoded are associated with 185 biological functions relevant to tumorigenesis

[75]

piR-017061

Downregulated

PDAC

–

[76]

125 piRNAs

Upregulated

AD

Target LIN7C, RAB11A, CYCS and KPNA6

[77]

103 piRNAs

Misregulated. Potential risk biomarkers

AD

–

[79]

105 piRNAs

Misregulated

transient focal ischemia

–

[80]

287 piRNAs

Upregulated

Mecp2 null brain (model for RTT)

–

[81]

22 piRNAs

piR-2106027

Misregualted

Upregulated

Potential diagnostic marker

Cardiac hypertrophy

–

[82]

959 piRNAs

951 piRNAs are downregulated 8 piRNAs are upregulated

Non-obstructive azoospermia

Putative targets are involved in cellular events such as cell proliferation apoptosis and differentiation

[87]

347 piRNAs

128 piRNAs are upregulated and 219 piRNAs are downregulated in islets from GK rats

Diabetes

Putative targets of piR- DQ732700 and piR- DQ746748 are involved in insulin secretion, insulin action or carbohydrate digestion

[88]

24 piRNAs

Misregulated

UL

–

[89]

  1. Different piRNAs/PIWI proteins as well as their corresponding features such as associated disease/abnormality, clinical relevance, proofed/putative molecular mechanisms and references are listed. For more than 8 piRNAs, only the number of piRNAs was shown in the table. The detailed piRNA species could be found in the corresponding references
  2. Short dashes indicate that the molecular mechanisms still remains elusive. N/A indicates not applicable