Xiaofeng Yang

FAM83A has a pro‐tumor function in ovarian cancer by affecting the Akt/Wnt/β‐catenin pathway

AbstractFamily with sequence similarity 83, member A (FAM83A) is a tumor‐exclusive gene that has a vital role in numerous tumors. However, its role in tumorigenesis remains controversial. This work is dedicated to the study of the role of FAM83A in ovarian cancer. We observed elevated levels of FAM83A in ovarian cancer specimens and cells. Kaplan–Meier survival curves revealed that elevated FAM83A levels predicted a worse overall survival in ovarian cancer patients. The inhibition of FAM83A caused remarkable suppressive effects on the proliferation and invasion of ovarian cancer cells, and enhanced their chemosensitivity. On the contrary, the upregulation of FAM83A had opposite effects. Mechanistically, FAM83A had an effect on the Akt and Wnt/β‐catenin pathways in ovarian cancer cells. The repression of Akt could cancel the regulatory effect of FAM83A overexpression on the Wnt/β‐catenin pathway. Moreover, reactivation of the Wnt/β‐catenin pathway abolished FAM83A‐inhibition‐evoked antitumor effects. Additionally, FAM83A inhibition weakened the tumorigenic potential of ovarian cancer in vivo. Taken together, this work shows that FAM83A exerts a pro‐tumor function in ovarian cancer by affecting the Akt/Wnt/β‐catenin pathway and proposes FAM83A as an effective and possible treatment target for ovarian cancer.

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.

FAM64A contributes to ovarian cancer proliferation and metastasis by suppressing TWIST1 ubiquitination and degradation

Ovarian cancer is among the most common cancers among gynecological malignancies. FAM64A is associated with various cancer progressions, but its function and mechanism in ovarian cancer remain unclear. We analyzed and examined the expression of FAM64A in ovarian cancer cells and tissues. Proliferation, migration and invasion were assessed by knocking down and overexpressing FAM64A in A2780 and SKOV3 cells, respectively. Bioinformatics combined with molecular experiments validated the molecular mechanism of FAM64A. A xenograft tumor model and lung metastasis model were created to explore the impact of FAM64A on tumor growth and metastasis in nude mice. To evaluate the relative signaling molecule expression, immunohistochemistry (IHC) and western blot assays were conducted. FAM64A was upregulated in ovarian cancer tissues and cells and was demonstrated to promote the proliferation, migration and invasion of A2780 and SKOV3 cells in vitro. Bioinformatics and western blot assays indicated that FAM64A could regulate the EMT-related transcription factor TWIST1 by suppressing TWIST1 ubiquitination and degradation via the E3 ubiquitin ligase STUB1. Moreover, the knockdown of FAM64A inhibited tumor growth in xenograft tumor mice and lung metastasis in vivo. FAM64A exerts its oncogenic function by regulating TWIST1 ubiquitination and degradation, indicating that FAM64A may provide a promising therapeutic target for the treatment of ovarian cancer.