MicroRNA-192-5p Promote the Proliferation and Metastasis of Hepatocellular Carcinoma Cell by Targeting SEMA3A

Abstract

Side population (SP) cells are a small subset of cells isolated from a cultured cancer cell line with characteristics similar to those of cancer stem cells, such as high metastatic and tumorigenic potentials. However, the molecular mechanisms remain unclear for the malignant properties of SP cells. In this study, SP cells were isolated by staining cultured HCCLM3 cells with fluorescent DNA-binding dye Hoechst 33342 and sorted by flow cytometry. The proportion of SP cells was 2.79%±0.19% in the HCCLM3 cell line. Compared with non-SP cells, SP cells possessed stronger capability of sphere formation and tumorigenicity, and expressed higher levels of CD133 and CD90. Then, we found that SP cells possessed 25 upregulated and 34 downregulated microRNAs with differences of >3-fold. As one of the upregulated microRNAs, miR-192-5p was computationally predicted to target semaphorin 3A (SEMA3A), a potent suppressor of tumor angiogenesis in various cancer models. Luciferase reporter assay showed that SEMA3A was a direct target of miR-192-5p. Overexpression of miR-192-5p promoted cell proliferation and metastasis targeting SEMA3A in HCCLM3 cells. Immunohistochemical staining revealed that SEMA3A expression was significantly reverse associated with metastasis in hepatocellular carcinoma tissues. The results indicate that miR-192-5p contributes to targeting SEMA3A in HCCLM3 cells, and this may be used as a target in targeted therapy and a marker for cancer behavior and prognosis.

Identification of a six‐miRNA panel in serum benefiting pancreatic cancer diagnosis

“…In liver fluke‐associated cholangiocarcinoma, serum miR‐192‐5p level was also elevated and might be involved in tumor genesis, metastasis, and poor survival . For some cancers such as hepatocellular carcinoma, bladder cancer, and non‐small cell lung cancer, miR‐192‐5p could act as a promoter of tumor proliferation and metastasis by targeting semaphorin 3A, Yin Yang 1, and the PI3K/Akt pathway, respectively . Besides, the other three upregulated serum miRNAs (let‐7b‐5p, miR‐223‐3p, and miR‐25‐3p) have also been reported to be associated with various cancer types, including prostate cancer, ovarian cancer, lung cancer, multiple myeloma, and anaplastic thyroid carcinoma .…”

miR-192 Is Overexpressed and Promotes Cell Proliferation in Prostate Cancer

“…miR-192 could act as either an oncogene or a tumor suppressor in human cancers. For example, miR-192 promotes the proliferation of cancer cell in hepatocellular carcinoma [17] and esophageal squamous cell carcinoma [18] by inhibiting their targets. However, miR-192 inhibits cell proliferation of bladder cancer cells via targeting cyclin D1, p21, p27, Bcl-2, Bax, and Mcl-1 [14].…”

“…However, the roles of miR-192 in tumor progression remain uncertain, and miR-192 could act as an oncogene. In hepatocellular carcinoma, miR-192 promotes the proliferation and metastasis of cancer cells by targeting SEMA3A [17]. miR-192 also promotes proliferation in esophageal squamous cell carcinoma by targeting Bim [18].…”

A five‐miRNA expression signature predicts survival in hepatocellular carcinoma

“…Inhibition of miR‐21 increases the expression of phosphatase and tensin homolog (PTEN), and induces cell apoptosis and decreases tumor cell proliferation, migration, and invasion in HCC cells . Overexpression of miR‐192‐5p promotes cell proliferation and metastasis by targeting SEMA3A in HCC cells . miR‐122 induces mesenchymal–epithelial transition and inhibits cell migration and invasion of HCC by targeting RhoA .…”

“…Overexpression of miR-192-5p promotes cell proliferation and metastasis by targeting SEMA3A in HCC cells (9). miR-122 induces mesenchymal-epithelial transition and inhibits cell migration and invasion of HCC by targeting RhoA (10).…”