MicroRNA‑130a regulated by HPV18 E6 promotes proliferation and invasion of cervical cancer cells by targeting TIMP2

Abstract

Human papillomaviruses (HPVs) have important roles in the development and progression of cervical cancer, but the underlying mechanisms are yet to be fully elucidated. MicroRNA-130a (miR-130a) has previously been reported to promote cervical cancer growth. However, the underlying molecular mechanisms by which miR-130a promotes cervical cancer progression have remained largely elusive. In the present study, polymerase chain reaction and western blot analyses were performed to examine the expression levels of miR-130a and associated proteins. A wound healing assay and a Transwell assay were applied to study cell migration and invasion. A luciferase reporter gene assay was performed to confirm the targeting associations of miR-130a. It was observed that miR-130a was significantly upregulated in cervical cancer tissues compared with that in adjacent non-tumorous tissues. High expression of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of cervical cancer. Furthermore, the expression of miR-130a was also higher in HPV(+) cervical cancer cell lines compared with that in HPV(-) cells. Knockdown of HPV18 E6 significantly inhibited the expression of miR-130a in HeLa cervical cancer cells. Furthermore, knockdown of miR-130a reduced the migration and invasion of HeLa cells. Tissue inhibitor of metalloproteinase 2 (TIMP2), an antagonist of matrix metalloproteinase 2 (MMP2), was identified as a novel, direct target gene of miR-130a. The expression of TIMP2 was negatively mediated by miR-130a, and HPV18 E6 inhibited the expression of TIMP2 in HeLa cells. Furthermore, knockdown of TIMP2 rescued the suppressive effects of miR-130a downregulation on the migration and invasion of HeLa cells. In summary, the present study suggests that HPV18 E6 promotes the expression of miR-130a, which further inhibits the expression of TIMP2 and promotes cervical cancer cell invasion. Therefore, HPV/miR-130a/TIMP2 signaling may be a potential target for the prevention of cervical cancer metastasis.

miR‑130a‑3p promotes cell proliferation and invasion by targeting estrogen receptor α and androgen receptor in cervical cancer

“…To date, the role of miR-130a in the progression of CC carcinogenesis is not completely understood. Yin et al ( 40 ) reported that high expression of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of CC. The results of the present study indicated that the expression of miR-130a in CC tissues was obviously higher compared with healthy cervical tissues, and miR-130a knockdown inhibited CC cell proliferation and invasion in vitro and in vivo compared with miR-130ai NC and control antagomiR, respectively.…”

MicroRNA‑130a‑3p promotes the proliferation and inhibits the apoptosis of cervical cancer cells via negative regulation of RUNX3

“…a previous study demonstrated that the mir-130 family (mir-130b, mir-301a and mir-301b) promoted the migration and invasion of bladder cancer cells via negative regulation of phosphatase and tensin homolog (PTen) (18). Jiang et al (29) revealed that mir-130a promoted the proliferation, migration and invasion of gastric cancer cells via targeting runX3, and Yin et al (28) verified that miR-130a enhanced the proliferation and invasion of cc cells via modulating TiMP2. in accordance with the results of these previous studies, in the present study it was concluded that the upregulation of mir-130a-3p contributed to the progression of cc.…”

“…chen et al (27) reported that upregulation of mir-130a expression was associated with the TnM stage and lymph node metastasis of colorectal cancer. Yin et al (28) demonstrated that upregulation of miR-130a was significantly associated with lymph node metastasis and an advanced clinical stage of cc. consistent with these previous studies, the present study demonstrated that high expression of mir-130a-3p was significantly associated with the FiGo stage, lymph node metastasis and depth of cervical invasion in patients with cc.…”

Downregulated miR‑130a enhances the sensitivity of acute myeloid leukemia cells to Adriamycin

“…mir-130a has been reported to promote cancer growth (16). Yin et al (17) reported that the upregulation of mir-130a was highly correlated with advanced clinical stage and lymph node metastasis in cervical cancer. Therefore, inhibition of mir-130a expression may represent a treatment strategy with potentially antileukemic effects.…”