MicroRNA‑203a‑3p is a candidate tumor suppressor that targets thrombospondin 2 in colorectal carcinoma

Abstract

The aim of the present study was to investigate the role of miR-203a-3p in colorectal cancer (CRC) and identify the target gene of microRNA (miR)-203a-3p. A total of 59 sets of cancer tissues and corresponding adjacent non-tumor tissues were collected from CRC patients (aged 31-78 years) between October 2016 and May 2017. Total RNA extraction and reverse transcription-quantitative polymerase chain reaction analysis, transfection assay, and Transwell and apoptosis assays, western blot analysis, a luciferase reporter assay and immunohistochemistry were performed. miR-203a-3p was found to be significantly downregulated in CRC tissues compared with adjacent normal tissues. The overexpression of miR-203a-3p was shown to inhibit the invasion and migration of human CRC SW480 and HT29 cells, and increase their apoptosis rates. Furthermore, miR-203a-3p downregulated the expression of thrombospondin 2 (THBS2) in SW480 and HT29 cells. It was also experimentally demonstrated that miR-203a-3p binds to the 3'-untranslated region of THBS2, downregulating THBS2 expression and thereby inhibiting CRC progression and metastasis. The expression of miR-203a-3p, which serves a tumor-suppressive role, in CRC tissues was significantly downregulated. As miR-203a-3p was determined to target THBS2 to inhibit CRC progression and metastasis; thus, miR-203a-3p may be considered as a potential novel approach to treating CRC.

Predominant Distribution of the RNAi Machinery at Apical Adherens Junctions in Colonic Epithelia Is Disrupted in Cancer

“…In addition, PLEKHA7 re-expression results in the increased levels of miRNAs that we have previously identified to be regulated by PLEKHA7 in Caco2 cells, such as miR-30b, miR-200c, and miR-203a ( Figure 5I) [10,25]. These miRNAs are well-established tumor suppressors and are downregulated in many cancers, including colorectal tumors, as well as in colon cancer cell lines, such as those included in our study [38][39][40][41][42][43][44][45][46][47][48][49][50][51]. Together, these results are in agreement with our previous findings [10,25] and further support a tumor suppressing role for PLEKHA7 in the colonic epithelium, through recruitment and regulation of the RNAi machinery.…”

Extracellular Matrix Biomarkers in Colorectal Cancer

“…Elevated ECM proteins in the tumor microenvironment increase the stiffness of the ECM, affecting cellular functions such as proliferation, adhesion, migration, tissue remodeling, and regulation of immune system [9][10][11]208]. [176,[179][180][181][182][183][184][185][186][187][188][189][190][191][192][193]195,196,[198][199][200][201][202]206] Collagen has important implications in the structural growth of tissue and regulates molecular signaling processes. A variety of tumors have been shown to overexpress collagen and its proteolytic components have been linked to increased invasiveness of tumors [41,84].…”

“…Differing from these results, Yosida et al reported that THBS2, regarded as an angiostatic factor, was significantly increased in CRC but not THBS1 [191]. In the opposite way to THBS1 regulation by miR-194, THBS2 has a binding domain in its 3 -untranslated region for miR-203a-3p, and downregulation of THBS2 by miR203a-3p inhibits CRC progression and metastasis [192]. There were also ambiguous results in terms of THBS2 expression such that low THBS2 expression reflected poor prognostic factors [193], while there was no correlation with improvement in metastatic colorectal cancer [194].…”

Identification of A Four-Microrna Panel in Serum As Promising Biomarker for Colorectal Carcinoma Detection

“…However, Qian et al suggested that miR-203a-3p was downregulated in CRC tissues compared with adjacent normal tissues. miR-203a-3p served as a tumor suppressor of CRC cells by downregulating THBS2 expression [21]. Both studies used CRC cell lines SW480 and SW620, but their conclusions contradicted each other.…”