MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer
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ORIGINAL ARTICLE
MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer Jingli Wu 1 & Yuying Zhao 1 & Fenglian Li 2 & Baohua Qiao 1 Received: 19 February 2019 / Accepted: 8 April 2019 # University of Navarra 2019
Abstract Cervical cancer is the third most common gynecologic cancer in the world. Exploration of the molecular mechanism underlying cervical cancer pathogenesis will provide new insights into the development of novel therapies. In this study, we were aimed to characterize a novel miRNA in cervical cancer tumorigenesis. First, we measured the expressional change of miR-144-3p in clinical tissues and cancer cells. Second, we employed cell proliferation, cell migration, and invasion assays to understand its functional role in cervical cancer. Then, we confirmed in vitro findings in xenograft cancer model. Last, we mapped out a downstream target of miR-144-3p and validated its functional role in cancer cells. In the results, miR-144-3p was found significantly downregulated in cervical cancer cells and tissues. Over-expressing miR-144-3p suppressed cancer cells growth and metastasis. Consistent with in vitro results, over-expressing miR-144-3p led to tumor growth inhibition in vivo. Further on, MAPK6 was identified as an endogenous target of miR-144-3p in cervical cancer. Knocking down MAPK6 inhibited cervical cancer cells proliferation, migration, and invasion potential. Our investigation was the first time to report miR-144-3p as a tumor suppressive miRNA in cervical cancer. It inhibited tumor growth by targeting MAKP6. The newly identified signalling axis may serve as novel therapeutic targets to manage cervical cancer. Keywords Cervical cancer . miR-144-3p . MAPK6 . Hela . HCC94
Introduction Cervical cancer is one of the major causes of cancer death among the women worldwide. About 90% of the deaths caused by cervical cancer were reported from developing countries. It is estimated about 530,000 new cases diagnosed annually. The average age as being diagnosed is 47 years [23]. Most cervical cancers are caused by human papilloma virus (HPV) infection. Viral DNA can integrate into the host genome DNA to activate oncogenic transformation. There are more than 100 subtypes of HPV. Among them, HPV16 and HPV18 are most commonly associated with the occurrence of cervical cancer. Other than HPV infection, age,
* Baohua Qiao [email protected] 1
Heze Municipal Hospital, No. 2888, Caozhou Road, Heze 274000, Shandong, China
2
The Second People’s Hospital of Caoxian County, Yuanqian Street, Qingguji Town, Caoxian County, Heze 274400, Shandong, China
smoking, using oral contraceptives, and exposure to diethylstilboestrol may be associated with increased risk of developing cervical cancer [5, 12]. It takes 10–15 years before cervical intraepithelial neoplasia turns into invasive cancer. Detecting the cervical neoplasia at the early stage usually lead to a better management to prevent and treat the development of cervical cancer. The discovery of the link between HPV infection and cervical canc
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