Ting Yang

MiR‐216a‐3p suppresses the proliferation and invasion of cervical cancer through downregulation of ACTL6A‐mediated YAP signaling

AbstractThe tumor‐suppressive role of microRNA‐216a‐3p (miR‐216a‐3p) has been evidenced in multiple tumors. Yet, the relevance of miR‐216a‐3p in cervical cancer remains undermined. The current study was designed to determine the expression and potential function of miR‐216a‐3p in cervical cancer. Expression of miR‐216a‐3p was markedly decreased in cervical cancer and functional assays revealed an inhibitory effect of miR‐216a‐3p on the proliferation, colony formation, and invasion of cervical cancer. Actin‐like 6A (ACTL6A) was identified as a target gene of miR‐216a‐3p. Elevated ACTL6A expression was detected in cervical cancer, and ACTL6A inhibition exhibited a tumor‐suppressive effect. ACTL6A inhibition increased yes‐associated protein (YAP) phosphorylation and downregulated YAP‐mediated transcriptional activity. ACTL6A restoration or YAP reactivation partially abrogated the miR‐216a‐3p‐mediated antitumor effect in cervical cancer cells. Taken together, these data demonstrate that miR‐216a‐3p acts as a potential tumor‐suppressive miRNA in cervical cancer, which exerts its function through inhibition of YAP signaling via targeting ACTL6A.

Human Papillomavirus E7 Oncoprotein Promotes Proliferation and Migration through the Transcription Factor E2F1 in Cervical Cancer Cells

Background: High-Risk Human Papillomavirus (HR-HPV) persistent infection is the main cause of cervical cancer and its precancerous lesions. A previous study showed that HPV16 and HPV58 infections were the most common infection types in the local region. Some studies also declared that HPV58 E7 variants increased the risk of cervical cancer among Asian populations. Objective: This study aimed to determine whether the HPV58 E7 T20I (C632T) variant promotes the malignant behavior of cervical cancer cells and the underlying mechanism of the HR-HPV E7 oncoprotein involved in the development of cervical cancer. Methods: CCK-8 and clone formation assays were used to detect cell proliferation ability. Transwell assays and cell wound healing assays were used to evaluate cell migration ability. Targeted knockdown of E2F1 expression using specific siRNA, RT-qPCR and Western blot were performed to assess gene expression changes. A chromatin immunoprecipitation assay was used to verify that E2F1 interacted with the TOP2A promoter region. Results: HPV58 E7 and HPV58 E7M oncoproteins increased the proliferation and migration ability of cervical cancer cells. However, the HPV58 E7 T20I variant did not promote malignant behaviors compared with wildtype HPV58 E7. HPV E7 and E7M oncoproteins increased the expression of TOP2A, BIRC5 and E2F1, and knockdown of HPV E7 decreased their expression. Low E2F1 expression reduced the expression of TOP2A and BIRC5 and inhibited the proliferation and migration ability of cervical cancer cells. E2F1 interacted with the TOP2A gene promoter region to promote its transcriptional expression. Conclusions: The HPV58 E7 T20I variant did not promote malignant behaviors compared with wild-type HPV58 E7. The HR-HPV E7 oncoprotein enhanced the proliferation and migration of cervical cancer cells, which was considered to be due to the HPV E7 oncoprotein, increasing the expression of BIRC5 and TOP2A by upregulating the transcription factor E2F1.