A total 1,301 plant miRNAs, including 654 homologs, with at least one read presented in the sample were identified from the selected transcriptome sequencing runs. Count of the reads within each sample is available in (Additional file 1: Table S1). The relative abundance of these miRNAs were compared to detected human miRNAs. Among them we found a singular case, peu-MIR2910, can be found ubiquitously within the selected samples. In some samples, up to more than one thousand copy of peu-MIR2910 can be found, which is more abundant than most of the human miRNAs detected within the samples. Beside peu-MIR2910, up to hundreds of copies of peu-MIR2916 in 379 samples, peu-MIR2914 in 359 samples, and tae-MIR2018 in 353 samples were also found.

The detected plant miRNAs are not human originated or sample contamination

Sequence alignment of the detected plant miRNAs sequence onto human genome was performed with BLAST [13] and resulted in zero alignment hit. Alignment of the conventional adaptor sequences to the plant miRNAs also resulted with zero hits. Through this result we are convinced that these detected plant miRNA sequence were not originated from conserved human sequences or adaptors contamination.

The plant miRNA peu-MIR2910 is conserved within comestible plants

Among the 1,301 plant miRNAs detected in our collected samples, miR2910 presented in all the 404 examined runs in relatively high abundance. Assuming that the source of plant miRNAs present in human plasma originated from food ingestion, then miR2910 must be evolutionally conserved in a wide variable kinds of comestible plants.

From the reports of recent years we found that peu-MIR2910 was reported to be expressed within one of the model organism we used, Zea mays [14]. As one of the main grain consumed all over the world, maize can potentially the source of the miR2910 detected in the data sets. On the other hand, we also found that miR2910 is conserved within fruits and vegetables. Melon [15], Sorghum [16], tomato [17], tea [18] and oil palm [19] are also the potential source of miR2910. All these evidences support the assumption that the peu-MIR2910 present in the human plasma samples originate from food ingestion. On the other hand, peu-MIR2914 and peu-MIR2916 were also found conserved within oil palm [20]. Conserved tae-MIR2018 was found in wheat [21, 22].

Plant miR159 and miR168a were also detected in the examined samples

To verify the analysis result with previous reports, we examined the amount of detected miR159 and miR168a within the examined samples. As listed in the (Additional file 1: Table S1), despite presenting in relatively small amount (less than 4 copies), miR159 can be found in 32 samples while miR168a can be found in 7 samples. The difference might be result from the difference of the diet habit. Most of the examined samples were presumably collected from Wisconsin, USA [23]. The dietary habit of the subjects can be much different from the subjects collect in China [6] and California [11]. On the other hand, given the fact that only roughly 1% of all the adaptor trimmed reads can be aligned onto plant genomes, as well as the generally low concentration of miRNA within plasma samples, detection of the miR159 as well as miR168a in less than 4 copy within one sample can still be considered as supporting evidence of the two previous reports.

Human genes can potentially be targeted by peu-MIR2910 and other plant miRNAs

In the previous reports [6, 11], plant miRNAs present in human circulating system were proven to be able to target human genes through similar AGO protein correlated mechanism. Given the assumption that miRNAs with similar or same target seed sequences can target same sets of genes, we tested the similarity of plant miRNAs and human miRNAs in target seed regions.

Through the result of the target seed analysis, we found that despite the whole sequence, including the hairpin, of peu-MIR2910 cannot be aligned onto human genome, the 6mer and 7mer-A1 target seed sequences of miR2910, CCAACT and CCAACTA, is the same as hsa-miR-4259 and hsa-miR-4715-5p. Given the previously reported case of miR168a [6] and miR159 [11], we hypothesis that peu-MIR2910 within the circulating system can target human genes as well. From the 51 target genes of hsa-miR-4259 and hsa-miR-4715-5p reported in miRTarBase [24], and the mature sequence of miR2910, we found 10 possible target genes predicted through miRTar [12], as illustrated in Fig. 1. We found that miR2910 can potentially target on 5′ UTR of LIMA1, and the CDS of CTNND1, FOLR1, LBX1 STK38, FAM127B, PHF19, ZNF295, SPRY4 and MRRF.

Fig. 1 Predicted target human genes of abundant plant miRNAs. The predicted miR2910, miR2916 and miR2018 targets through miRTar [12] are illustrated in this figure. The pink diamond shape nodes represent plant miRNAs while the round blue nodes represent human genes Full size image

Interestingly, we also found that miR2916 has exact same 8mer target seed sequence, AGTCCCCA, with human miRNA hsa-miR-4652-5p. From the 40 target genes of hsa-miR-4652-5p reported in miRTarBase [24], and the mature sequence of miR2916, we found other 20 possible target genes predicted through miRTar [12]. Same analysis process was conducted on miR2018, and three potential human gene targets were found. These findings were also illustrated in Fig. 1.

From the gene sets enrichment, we found that LBX1, PHF19, STK36, ZNF295 and CTNND1 are associated with regulation of transcription, while SPRY 4 belongs to human JAK-STAT signaling pathway, as summarized in Table 1. CTNND1 is also associated with Adherens junctions and endocytosis [25]. We also found that three genes MEN1, LDB1 and TLX1, predicted to be targeted by miR2916 were associated with Transcriptional misregulation in cancer, as summarized in Table 2.

Table 1 Gene set enrichment of miR2910 target genes Full size table