Oncomirnas and Tumor Suppressors In Microvesicles From Four Types Of Cancer

Microvesicles (MVs) are small vesicles that are shed from almost all cell types including cancer cells into their surroundings. These secreted MVs bear surface receptors/ligands and miRNA of the original cells and play a role in cancer. Our aim in this study was to identify MVs miRNAs that might play important roles both in solid and non-solid tumors.

The MVs miRNA expression from 4 kinds of cancer cell lines (SMMC-7721, K562, Nalm6 and Jurkat) and healthy peripheral blood cells were analyzed by miRNA microarray. Quantitative real-time polymerase chain reaction (qRT-PCR) was further performed to verify the expression of 4 dysregulated miRNAs.

The miRNA microarray revealed aberrantly expressed miRNAs of MVs between the four types of cancer cells and normal cells. In the MVs from cancer groups, 73 miRNAs were up-regulated and 148 were down-regulated in all the four types of cancer cell lines, indicating that solid and non-solid tumors shared some dysregulated MVs miRNAs. qRT-PCR verified statistically consistent expression of four selected miRNAs with microarray analysis. The top six shared upregulated MVs miRNAs in the four cancer cells lines were miR-1290, miR-1268, miR-1246, miR-125a-3p, miR-1305, miR-1226*. The top seven shared downregulated MVs miRNAs in the four cancer cells lines were miR-335, miR-1, miR-363, miR-122, miR-223, miR-338-3p and miR-340.

The general roles of the upregulated MVs miRNAs were oncomiRNAs in multicancer. MiR-1290 and its potential targets are associated with characteristics of estrogen receptor α-positive breast cancer. Up-regulations of miR-1290 impaired cytokinesis and affected the reprogramming of colon cancer cells. miR-1246 might serve as a likely link of the p53 family with Down syndrome and proposed a new p53-miR-1246-DYRK1A-NFAT pathway in cancer.

The functional roles of the downregulated MVs miRNAs were tumor suppressors in many kinds of cancer. MiR-335 acted as a candidate tumor suppressor and inhibited tumor reinitiation and represented an invasion suppressor gene by targeting Bcl-w in many kinds of cancer. HBx regulated miR-338-3p in HCC and miR-338-3p inhibited proliferation by regulating CyclinD1, and miR-338-3p suppressed the invasion of liver cancer cell by targeting smoothened gene in liver cancer. miR-340 inhibited of breast cancer cell migrations and invasions through targeting of oncoprotein c-Met and may play an important role in breast cancer progression.

Our study identifies oncomiRNAs and tumor suppressors in MVs from four types of cancer. These MVs miRNAs may contribute to the developments of solid and non-solid tumors and should be further evaluated as a novel biomarker for cancers and may provide potential targets for novel therapeutic strategies.

No relevant conflicts of interest to declare.