title: RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis.
abstract: A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma.
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Dermatology, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Zhengtai
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University Xiangya Road, Changsha, Hunan 410008, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Chenzhou NO. 1 People's Hospital Chenzhou, Hunan 423000, China.
authors.forename: Huijun
authors.initials: H
authors.lastname: Liao
mesh_terms: D000328:Adult; D000368:Aged; D051926:Basigin / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006019:Glycolysis / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering; D027981:Symporters / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D055815:Young Adult; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D051926:Basigin; D027501:Monocarboxylic Acid Transporters; D034741:RNA, Small Interfering; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C497886:BSG protein, human
keywords: CD147; RNA interference; Thyroid cancer-experimental; genetics; glycolysis; pathology-thyroid