Search

// Ya-Ping Ye 1, 2, 3, * , Ping Wu 1, 2, 3, * , Chun-cai Gu 1, 2, 3, * , Dan-ling Deng 1, 2, 3 , Hong-Li Jiao 1, 2, 3, Ting-Ting Li 1, 2, 3 , Shu-Yang Wang 1, 2, 3 , Yong-Xia Wang 1, 2, 3 , Zhi-Yuan Xiao 1, 2, 3 , Wen-ting Wei 1, 2, 3 , Yan-Ru Chen 1, 2, 3 , Jun-Feng Qiu 1, 2, 3 , Run-Wei Yang 1, 2, 3 , Jie Lin 1, 2, 3 , Li Liang 1, 2, 3 , Wen-Ting Liao 1, 2, 3 , Yan-Qing Ding 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 3 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China * These authors have contributed equally to this work Correspondence to: Wen-Ting Liao, email: liaowt2002@gmail.com Yan-Qing Ding, email: dyq@fimmu.com Keywords: miR-450b-5p, Wnt/β-Catenin pathway, colorectal cancer, progression, KRAS Received: May 13, 2016 Accepted: July 14, 2016 Published: August 2, 2016 ABSTRACT The development and progression of CRC are regarded as a complicated network and progressive event including genetic and/or epigenetic alterations. Recent researches revealed that MicroRNAs are biomarkers and regulators of CRC progression. Analyses of published microarray datasets revealed that miR-450b-5p was highly up-regulated in CRC tissues. In addition, high expression of miR-450b-5p was significantly associated with KRAS mutation. However, the role of miR-450b-5p in the progression of CRC remains unknown. Here, we sought to validate the expression of miR-450b-5p in CRC tissues and investigate the role and underlying mechanism of miR-450b-5p in the progression of CRC. The results revealed that miR-450b-5p was up-regulated in CRC tissues, high expression level of miR-450b-5p was positively associated with poor differentiation, advanced TNM classification and poor prognosis. Moreover, miR-450b-5p was especially high in KRAS-mutated cell lines and could be up-regulated by KRAS/AP-1 signaling. Functional validation revealed that overexpression of miR-450b-5p promoted cell proliferation and tumor growth while inhibited apoptosis of CRC cells. Furthermore, we demonstrated that miR-450b-5p directly bound the 3’-UTRs of SFRP2 and SIAH1, and activated Wnt/β-Catenin signaling. In conclusion, miR-450b-5p induced by oncogenic KRAS is required for colorectal cancer progression. Collectively, our work helped to understand the precise role of miR-450b-5p in the progression of CRC, and might promote the development of new therapeutic strategies against CRC.

// Huijun Xie 1, 2, 3, * , Xiaoli Ren 1, 2, 3, * , Sainan Xin 1, 2, 3, * , Xiaoliang Lan 4 , Guifeng Lu 1, 2, 3 , Yuan Lin 1, 2, 3 , Shaoshan Yang 1, 2, 3 , Zhicheng Zeng 1, 2, 3 , Wenting Liao 1, 2, 3 , Yan-Qing Ding 1, 2, 3 , Li Liang 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Guangzhou, Guangdong, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 3 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China 4 Department of General Surgery, Nanfang Hospital, Guangzhou, Guangdong, China * These authors contributed equally to this work Correspondence to: Li Liang, email: redsnow007@hotmail.com Yan-Qing Ding, email: dyq@fimmu.com Keywords: hsa_circ_001569, miR-145, colorectal cancer, FMNL2, BAG4 Received: December 08, 2015 Accepted: March 07, 2016 Published: April 05, 2016 ABSTRACT Circular RNAs (circRNAs), a large class of RNAs, have recently shown huge capabilities as gene regulators in mammals. Some of them bind with microRNAs (miRNAs) and act as natural miRNA sponges to inhibit related miRNAs’ activities. Here we showed that hsa_circ_001569 acted as a positive regulator in cell proliferation and invasion of colorectal cancer (CRC). Moreover, hsa_circ_001569 was identified as a sponge of miR-145 and up-regulated miR-145 functional targets E2F5, BAG4 and FMNL2. In CRC tissues, circ_001569 negatively correlated with miR-145, and miR-145 correlated negatively with E2F5, BAG4 and FMNL2 expressions. Our study reveals a novel regulatory mechanism of circ_001569 in cell proliferation and invasion in CRC, provides a comprehensive landscape of circ_001569 that will facilitate further biomarker discoveries in the progression of CRC.

DAB2IP has been identified as a tumor suppressor in several cancers but its oncogenic role and transcriptionally regulatory mechanisms in the progression of colorectal carcinoma (CRC) remain unknown. In this study, DAB2IP was down-regulated in CRC tissues and a valuable prognostic marker for survival of CRC patients, especially in the late stage. Moreover, DAB2IP was sufficient to suppress proliferation, epithelial-mesenchymal transition (EMT), invasion and metastasis in CRC. Mechanically, the linear complex of EZH2/HDAC1/Snail contributed to DAB2IP silencing in CRC cells. The study further proved that the positive feedback loop between Snail and DAB2IP existed in CRC cells and DAB2IP was required for Snail-induced aggressive cell behaviors. Finally, DAB2IP correlated negatively with Snail and EZH2 expressions in CRC tissues. Our findings reveal the suppressive role and a novel regulatory mechanism of DAB2IP expression in the progression of CRC. DAB2IP may be a potential, novel therapeutic and prognostic target for clinical CRC patients.

// Yuling Li 1,2,* , Zhenbing Lv 1,3,4,* , Guoyang He 1,2 , Jianmei Wang 1,2 , Xiaojing Zhang 1,5 , Guifeng Lu 1,2 , Xiaoli Ren 1,2 , Feifei Wang 1,2 , Xiaohui Zhu 1,2 , Yi Ding 6 , Wenting Liao 1,2 , Yanqing Ding 1,2 and Li Liang 1,2 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China 2 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong Province, People’s Republic of China 3 Department of General Surgery Two, Nanchong Central Hospital, Nanchong city, Sichuan Province, People’s Republic of China 4 The Second Clinical School of Northern Sichuan Medical College, Nanchong city, Sichuan Province, People’s Republic of China 5 Department of Pathology, Shenzhen University, Shenzhen, People’s Republic of China 6 Department of Radiotherapy, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China * These authors contributed equally to this work Correspondence to: Li Liang, email: // Keywords : miR-371-5p, SOX17, SOX2, metastasis, colorectal cancer Received : January 15, 2015 Accepted : February 10, 2015 Published : March 15, 2015 Abstract Cancer stem cells (CSCs) and EMT-type cells, which share molecular characteristics with CSCs, have been believed to play critical roles in tumor metastasis. Although much progress has been garnered in elucidating the molecular pathways that trigger EMT, stemness and metastasis, a number of key mechanistic gaps remain elusive. In the study, miR-371-5p was obviously down-regulated in primary CRC tissues compared with matched adjacent normal mucosa and correlated significantly with differentiation, tumor size, lymphatic and liver metastases. MiR-371-5p could attenuate proliferation, invasion in vitro and metastasis in vivo in CRC cells. It also suppressed EMT by regulating Wnt /β-catenin signaling and strongly decreased the CRC stemness phenotypes. Moreover, demethylation of SOX17 induced miR-371-5p expression and consequently suppressed its direct target SOX2 in CRC cells. MiR-371-5p was necessary for SOX17 mediated cancer-related traits and SOX2 was a functional target of miR-371-5p. A positive relationship between SOX17 and miR-371-5p expression and a negative one between miR-371-5p and SOX2 expression were observed in CRC cell lines and tissues. In conclusion, we identified miR-371-5p as an important “oncosuppressor” in CRC progression and elucidated a novel mechanism of the SOX17/miR-371-5p/SOX2 axis in the regulation of EMT, stemness and metastasis, which may be a potential therapeutic target.

// Yong-Xia Wang 1, 2, 3, 4, * , Yan-Ru Chen 1, 2, 3, * , Shan-Shan Liu 1, 2, 3, * , Ya-Ping Ye 1, 2, 3 , Hong-Li Jiao 1, 2, 3 , Shu-Yang Wang 1, 2, 3 , Zhi-Yuan Xiao 1, 2, 3 , Wen-Ting Wei 1, 2, 3 , Jun-Feng Qiu 1, 2, 3 , Li Liang 1, 2, 3 , Wen-Ting Liao 1, 2, 3 , Yan-Qing Ding 1, 2, 3 1 Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China 2 Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China 3 Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou, Guangdong, China 4 Department of Pathology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan, China * These authors have contributed equally to this work Correspondence to: Wen-Ting Liao: email: liaowt2002@gmail.com Yan-Qing Ding: email: dyq@fimmu.com Keywords: colorectal cancer, MiR-384, metastasis, KRAS, CDC42 Received: July 20, 2016 Accepted: October 03, 2016 Published: October 17, 2016 ABSTRACT Colorectal cancer (CRC) is the third most common cancer worldwide. Metastatic progression is a primary factor contributing to lethality of CRC patients. However, the molecular mechanisms forming early local invasion and distant metastatic colonies are still unclear and the present therapeutic approaches for CRC are unsatisfactory. Therefore, novel therapies targeting metastatic invasion that could prevent tumor spreading and recurrence are urgently needed. Our study showed that the decrease of miR-384 was found in 83.0% (83/100) CRC patients. And low-leveled expression of miR-384 was closely correlated with the invasive depth, lymph node and distant metastasis of CRC. Overexpression of miR-384 could inhibit the invasive and migrating abilities of CRC cells in vitro and the metastatic potential in vivo . Luciferase assays showed that miR-384 repressed the expression of Kirsten Ras (KRAS) and Cell division cycle 42 (CDC42) by directly targeting their 3’-untranslated regions. There is functional and mechanistic relationship between miRNA-384 and KRAS, CDC42 in the invasion and metastasis of CRC. And our findings suggest that miR-384could be a potent therapeutic target for CRC. Restoration of miR-384 expression might provide novel therapeutic approach to the reduction of CRC metastasis.