This study is the first to suggest that HOTAIR plays an important role in the carcinogenesis of endometrial cancer. Targeting HOTAIR may be a novel therapeutic strategy for endometrial cancer.

Fatty acid-binding protein 5 (FABP5) was found in our previous study to be a potential biomarker for lymph node metastasis of cervical cancer. However, the roles of FABP5 in cervical cancer remain unclear. In the present study, FABP5 expression was found to be significantly upregulated in cervical cancer tissues, and high FABP5 expression was significantly correlated with lymph node metastasis, lymphovascular space invasion, the International Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size. Moreover, FABP5 was an independent factor for poor prognosis in cervical cancer patients. Silencing of FABP5 inhibited cell proliferation, colony formation, cell migration, and invasion in vitro. Furthermore, FABP5 silencing significantly reduced tumor growth and lung metastases in a murine allograft model in vivo. In addition, FABP5 silencing decreased the expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in vitro and in vivo. Collectively, these findings indicated that FABP5 plays an important role in the carcinogenesis and metastasis of cervical cancer, and FABP5 may be a novel predictor for prognostic assessment of cervical cancer patients.

Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. Clarification of the detailed mechanisms underlying LNM may provide potential clinical therapeutic targets for CC patients with LNM. However, the molecular mechanism of LNM in CC is unclear. In the present study, we demonstrated that fatty acid synthase (FASN), one of the key enzymes in lipid metabolism, had upregulated expression in the CC samples and was correlated with LNM. Moreover, multivariate Cox proportional hazards analysis identified FASN as an independent prognostic factor of CC patients. Furthermore, gain-of-function and loss-of-function approaches showed that FASN promoted CC cell migration, invasion, and lymphangiogenesis. Mechanistically, on the one hand, FASN could regulate cholesterol reprogramming and then activate the lipid raft-related c-Src/AKT/FAK signaling pathway, leading to enhanced cell migration and invasion. On the other hand, FASN induced lymphangiogenesis by secreting PDGF-AA/IGFBP3. More importantly, knockdown of FASN with FASN shRNA or the inhibitors C75 and Cerulenin dramatically diminished LNM in vivo, suggesting that FASN plays an essential role in LNM of CC and the clinical application potential of FASN inhibitors. Taken together, our findings uncover a novel molecular mechanism in LNM of CC and identify FASN as a novel prognostic factor and potential therapeutic target for LNM in CC.

Previous studies have demonstrated the involvement of nerve repellent factors in regulation of the imbalanced innervation of endometriosis. This prospective study aims to explore the role of Sema 3A in regulating aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis. Ectopic endometriotic lesion were collected from patients with peritoneal endometriosis (n = 24) and deep infiltrating endometriosis of uterosacral ligament (n = 20) undergoing surgery for endometriosis. Eutopic endometrial samples were collected from patients with endometriosis (n = 22) or without endometriosis (n = 26). Healthy peritoneum (n = 13) from the lateral pelvic wall and healthy uterosacral ligament (n = 13) were obtained from patients who had no surgical and histological proof of endometriosis during hysterectomy for uterine fibroids. Firstly, we studied the immunostaining of Sema 3A, Plexin A1 and NRP-1 in all the tissues described above. Then we studied the nerve fiber density (NFD) of endometriosis-associated (sympathetic) nerve and para-endometriotic (sympathetic) nerve by double immunofluorescence staining. Finally we analyzed the relationship between expression of Sema 3A in stromal cells of endometriotic lesion and the aberrant innervation of endometriosis. Semi-quantitative immunostaining demonstrated that (1) Higher immunostaining of Sema 3A were found in the eutopic endometrial glandular epithelial cells from patients with endometriosis (p = 0.041) than those without endometriosis; (2) Sema 3A immunostaining was higher in glandular epithelial cells of peritoneal endometriosis (P<0.001) and deep infiltrating endometriotic lesions of uterosacral ligament (P = 0.028)compared with glandular epithelial cells of the endometrium from women with endometriosis, while its expression in ectopic stormal cells in both groups were significantly lower than that from eutopic endometrium of women without endometirosis (P<0.001, P<0.001, respectively). NFDs of Anti-TH (+) endometriosis-associated sympathetic nerve of peritoneal endometriosis (p<0.001) and deep endometriosis of uterosacral ligament (p<0.001) were significantly lower than NFDs of para-endometriotic sympathetic nerve. Our results suggest that Sema 3A may contribute to the regulation of aberrant sympathetic innervation in peritoneal and deep infiltrating endometriosis.

The prognosis for cervical cancer (CCa) patients with lymph node metastasis (LNM) is dismal. Elucidation of the molecular mechanisms underlying LNM may provide clinical therapeutic strategies for CCa patients with LNM. However, the precise mechanism of LNM in CCa remains unclear. Herein, we demonstrated that protein tyrosine phosphatase receptor type M (PTPRM), identified from TCGA dataset, was markedly upregulated in CCa with LNM and correlated with LNM. Moreover, PTPRM was an independent prognostic factor of CCa patients in multivariate Cox′s proportional hazards model analysis and associated with poor prognosis. Furthermore, through gain-of-function and loss-of-function approaches, we found that PTPRM promoted CCa cells proliferation, migration, invasion, lymphangiogenesis, and LNM. Mechanistically, PTPRM promoted epithelial-mesenchymal transition (EMT) via Src-AKT signaling pathway and induced lymphangiogenesis in a VEGF-C dependent manner, resulting in LNM of CCa. Importantly, knockdown of PTPRM dramatically reduced LNM in vivo, suggesting that PTPRM plays an important role in the LNM of CCa. Taken together, our findings uncover a novel molecular mechanism in the LNM of CCa and identify PTPRM as a novel prognostic factor and potential therapeutic target for LNM in CCa.