TAGLN2 promotes the proliferation, invasion, migration and epithelial‑mesenchymal transition of colorectal cancer cells by activating STAT3 signaling through ANXA2

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer-associated mortality worldwide and currently ranks third in the USA in terms of prevalence. Transgelin-2 (TAGLN2) was previously reported to serve as a tumor promoter in various types of cancer. The present study aimed to investigate the role of TAGLN2 in the progression of CRC and to determine the potential underlying mechanism. The expression level of TAGLN2 in CRC cells (HCT116, SNU-C1, LoVo and SW480) were first detected by reverse transcription quantitative PCR and western blotting. Following TAGLN2 knockdown through transfection with short hairpin (sh)RNAs against TAGLN2, CRC cell proliferation was determined using Cell Counting Kit-8 and 5'-ethynyl-2'-deoxyuridine assays. Cell migration and invasion were evaluated using wound healing and Transwell assays, respectively. The expression levels of matrix metalloproteinase (MMP)2, MMP9 and proteins associated with epithelial-mesenchymal transition (EMT), including N-cadherin (N-cad), vimentin, zinc finger E-box binding homeobox 2 (ZEB2) and E-cadherin (E-cad), were also evaluated by western blotting. Furthermore, following TAGLN2 overexpression and the use of signal transducer and activator of transcription 3 (STAT3) inhibitors to treat CRC cells, all the aforementioned biological parameters were evaluated. The potential relationship between annexin 2 (ANXA2) and STAT3 was confirmed by western blotting analysis. The expression level of TAGLN2 was found to be particularly high in CRC cells. Following TAGLN2 knockdown, CRC cell proliferation, migration, invasion and EMT were significantly inhibited. TAGLN2 knockdown also suppressed STAT3 phosphorylation in CRC cells. In addition, the promoting effects of TAGLN2 overexpression on the progression of CRC were reversed by STAT3 inhibitor. Furthermore, ANXA2 was positively associated with STAT3. Taken together, these findings demonstrated that TAGLN2 could promote the proliferation, invasion, migration and EMT of CRC cells by activating STAT3 and regulating ANXA2 expression. This may reveal the underlying mechanism by which TAGLN2 might regulate the progression of CRC and provide potential therapeutic targets for the treatment of CRC.

CpG Site-Based Signature Predicts Survival of Colorectal Cancer

“…To determine whether any of the most highly methylated genes discovered have been implicated in CRC, we performed in silico validation using published reports. Among the genes containing the top CpG sites shown in Table 1 are the genes ADAMTS2 , ADAMTS5 , ADARB2 , ADCY1 , ADHFE1 , AGRN , AKR1B1 , ANK1 , ANKRD13B , ANXA2 , AQP5 , ATP11A , BCAT1 , BEND5 , BOLL , CADM2 and CASR , which have been implicated in CRC [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. A complete list of all CpG sites significantly associated with CRC and the genes they map to, including DMRS in which they are located, is presented in Supplementary Table S1 .…”

“…The clinical significance of our investigation is that DNA methylation-based molecular markers have the promise for detection and clinical management of CRC. Although the DNA methylation biomarkers we discovered were not clinically validated, which could preclude their implementation in clinical practice, in silico validation revealed important aberrantly methylated genes including NPBWR1 , CDH12 , NR5A2 , DCLK1 , NKX2-2 , KIAA1026 , ADARB2 , MAGI2 , SMAD3 , GUCY1B3 , DOK6 , EFS and PCSK2 implicated in CRC [ 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ], suggesting that if further confirmed these genes could serve as prognostic markers. For example, the cadherin-12 ( CDH12 ) gene has been shown to increase cancer cell migration, invasion and progression via promoting EMT by targeting the transcriptional factor Snail [ 52 , 56 ].…”

Identification of Serum Biomarkers to Monitor Therapeutic Response in Intestinal-Type Gastric Cancer

“…Each of the markers we identified have previously been linked to human cancer, and thus are not limited in relevance to the murine model employed. Of these, Tagln2 has previously been linked to angiogenesis, proliferation, migration, and epithelial–mesenchymal transition in GC [ 25 , 26 ], while Mbl2 gene variants have been linked to risk of stomach cancer [ 27 ] and increased serum levels linked to pancreatic cancer [ 28 ]. In addition, Itih3 has previously been identified as a predictor of GC in mice and patients [ 29 ], while F12 is a prognostic marker for thyroid cancer [ 30 ].…”

Interaction of TAGLN and USP1 promotes ZEB1 ubiquitination degradation in UV-induced skin photoaging

“…Long-term exposure to UV rays causes the senescence-associated secretory phenotype (SASP) [ 20 ]. TAGLN is an actin-related protein, which is related to cell proliferation, migration, and invasion [ 21 , 22 ]. Studies on TAGLN found that its imbalance can promote the development of rectal, breast, and colorectal cancers, and is considered to be a tumor suppressor [ 23 – 26 ].…”