Background: This study is aim to profile the differentially expressed microRNAs (DEMs) of premenopausal endometrial cancer (EC), identify their target genes and understand their roles in carcinogenesis. Methods: Next-generation sequencing (NGS) was performed on 3 premenopausal EC and 3 premenopausal normal endometrial tissues. Selection of candidate miRNAs and subsequent validation were performed by qRT-PCR on 20 premenopausal EC, 30 premenopausal normal endometrial and 40 postmenopausal EC samples. The relationship between DEMs and clinical characteristics was analyzed. Results: 136 upregulated and 131 downregulated DEMs were identified. The expression of miR-1251-5p was highly upregulated in premenopausal EC samples compared with premenopausal normal endometrial samples and significantly downregulated compared with postmenopausal EC samples. The expression of miR-6892-5p was highly upregulated in premenopausal EC samples compared with premenopausal normal endometrial samples and postmenopausal EC samples. In the premenopausal EC group, miR-1251-5p expression was closely correlated with menarche age, number of pregnancies, tumor grading, myometrial infiltration and lymph node metastasis; miR-6892-5p expression was closely correlated with BMI, hypertension, tumor grading, and metastasis. Conclusions: miR-1251-5p and miR-6892-5p may play important roles in tumorigenesis progression of premenopausal EC.

Jing Zhang, Bin Li, Jialan Chen, Fei Wang, Yu Zhang, Lu Gan. Mir-1251-5p/Mir-6892-5p Expression with Clinicopathological Factors in Premenopausal Endometrial Cancer. Academic Journal of Medicine & Health Sciences (2022) Vol. 3, Issue 1: 22-31. https://doi.org/10.25236/AJMHS.2022.030105.

[1] Hutt Suzanna, Tailor Anil, Ellis Patricia, Michael Agnieszka, Butler-Manuel Simon, and Chatterjee Jayanta. (2019) The role of biomarkers in endometrial cancer and hyperplasia: a literature reviews. Acta Oncol, 58, 342-352. 

[2] Lyu Tianjiao, Guo Lu, Chen Xiaojun, Jia Nan, Gu Chao, Zhu Menghan, Zhao Yuqing, Liu Xiaoxia, and Feng Weiwei.Ovarian preservation for premenopausal women with early-stage endometrial cancer: a Chinese retrospective study. (2019) J Int Med Res, 47,2492-249

[3] Gao Yifei, Zhao Min, Dai Xujing, Tong Mancy, Wei Jia, and Chen Qi. The prevalence of endometrial cancer in pre- and postmenopausal Chinese women. (2016) Menopause, 23, 884-7. 

[4] Pennant M E, Mehta R, Moody P, Hackett G, Prentice A, Sharp S J, and Lakshman R Premenopausal abnormal uterine bleeding and risk of endometrial cancer. (2017) BJOG, 124, 404-411. 

[5] Wise Michelle R, Jordan Vanessa, Lagas Alice, Showell Marian, Wong Nicole, Lensen Sarah, and Farquhar Cynthia M. Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review. (2016) Am J Obstet Gynecol, 214, 689.e1-689.e17. 

[6] Mu Nan, Dong Mei, Liu Chunyan, Wang Xiuli, Cong Jianglin, Wang Liqian, Wang Xiaojie, Lakhani Ishan, Liu Xia, Jianqing Hou, Shaoguang Wang, and Gary Tse et al. Association between preoperative serum insulin levels and lymph node metastasis in endometrial cancer-a prospective cohort study. (2018) Cancer Med, 7, 1519-1527.

[7] Clarke MA, Long BJ, Sherman ME, Lemens MA, Podratz KC, Hopkins MR, Ahlberg LJ, Mc Guire LJ, Laughlin-Tommaso SK, Bakkum-Gamez JN, and Wentzensen N. Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms. (2020) Am J Obstet Gynecol. 223(4), 549.e1-549.e13. 

[8] Wright JD, Jorge S, Tergas AI, Hou JY, Burke WM, Huang Y, Hu JC, Ananth CV, Neugut AI, and Hershman DL. Utilization and Outcomes of Ovarian Conservation in Premenopausal Women with Endometrial Cancer. (2016) Obstet Gynecol, 127, 101-108. 

[9] Gonthier Clémentine, Douhnai Daria, Koskas Martin, Lymph node metastasis probability in young patients eligible for conservative management of endometrial cancer. (2020), Gynecol Oncol,157,131-135.

[10] Cortez MA, Anfossi S, Ramapriyan R, Menon H, Atalar SC, Aliru M, Welsh J, and Calin GA. Role of miRNAs in immune responses and immunotherapy in cancer. (2019) Genes Chromosomes Cancer, 58, 244-253. 

[11] Pardini Barbara, Sabo Alexandru Anton, Birolo Giovanni, and Calin George Adrian.Noncoding RNAs in Extracellular Fluids as Cancer Biomarkers: The New Frontier of Liquid Biopsies. (2019) Cancers (Basel), 11: undefined. 

[12] Delangle R, De Foucher T, Larsen AK, Sabbah M, Azaïs H, Bendifallah S, Daraï E, Ballester M, Mehats C, Uzan C, and Canlorbe G. The Use of microRNAs in the Management of Endometrial Cancer: A Meta-Analysis. (2019) Cancers (Basel), 11, undefined. 

[13] Wilczynski Milosz, Senderowska Daria, Krawczyk Tomasz, Szymanska Bozena, and Malinowski Andrzej. MiRNAs in endometrioid endometrial cancer metastatic loci derived from positive lymph nodes. (2020) Acta Obstet Gynecol Scand, 99,1085-1091. 

[14] Bibi F, Naseer MI, Alvi SA, Yasir M, Jiman-Fatani AA, Sawan A, Abuzenadah AM, Al-Qahtani MH, and Azhar EI. microRNA analysis of gastric cancer patients from Saudi Arabian population. (2016) BMC Genomics,17, 751

[15] Shao Yang, Liu Xiaomin, Meng Jiao, Zhang Xiaofei, Ma Zhongliang, and Yang Gong.MicroRNA-1251-5p Promotes Carcinogenesis and Autophagy via Targeting the Tumor Suppressor TBCC in Ovarian Cancer Cells. (2019) Mol Ther, 27, 1653-1664. 

[16] Han S, Wang L, Sun L, Wang Y, Yao B, Chen T, Liu R, and Liu Q. MicroRNA-1251-5p promotes tumor growth and metastasis of hepatocellular carcinoma by targeting AKAP12. (2020) Biomed Pharmacother, 122, 109754. 

[17] Liu T, Fang Y, Zhang H, Deng M, Gao B, Niu N, Yu J, Lee S, Kim J, Qin B, Xie F, Evans D, Wang L, Lou W, and Lou Z. HEATR1 Negatively Regulates Akt to Help Sensitize Pancreatic Cancer Cells to Chemotherapy. (2016) Cancer Res,76,572-81. 

[18] Goel Raghuveera Kumar, Lukong Kiven Erique, Understanding the cellular roles of Fyn-related kinase (FRK): implications in cancer biology. [J] .Cancer Metastasis Rev, 2016, 35: 179-99. 

[19] Hua L, Wang G, Wang Z, Fu J, Fang Z, Zhuang T, Zhao L, Zong Z, Ye C, Liu H, Zhu Y, Yu R. Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth. (2019) J Neurooncol,143,35-47. 

[20] Grill JI, Neumann J, Herbst A, Ofner A, Hiltwein F, Marschall MK, Zierahn H, Wolf E, Schneider MR, and Kolligs FT. Loss of DRO1/CCDC80 results in obesity and promotes adipocyte differentiation. (2017) Mol Cell Endocrinol, 439, 286-296. 

[21] Kang KW, Kim OS, Chin JY, Kim WH, Park SH, Choi YJ, Shin JH, Jung KT, Lim DS, Lee SK. Diastolic Dysfunction Induced by a High-Fat Diet Is Associated with Mitochondrial Abnormality and Adenosine Triphosphate Levels in Rats. (2015) Endocrinol Metab (Seoul), 30,557-68.