Regulatory effects of lncRNA ATB targeting miR‐200c on proliferation and apoptosis of colorectal cancer cells

Abstract

This investigation was intended to elucidate whether long noncoding RNA (lncRNA)‐activated by transforming growth factor‐β (ATB) interacting with miR‐200c could mediate colorectal cancer (CRC) progression, offering potential strategies for diagnosing and treating CRC. Here totally 315 patients with CRC were recruited, and their CRC tissues and adjacent normal tissues were gathered. Concurrently, four colon cancer cell lines (ie, SW620, Lovo, HCT116, and SW480) and the human colon mucosal epithelial cell line (NCM460) were also purchased. Moreover, si‐ATB, si‐NC, miR‐200c mimic, miR‐200c inhibitor, and miR‐NC were prepared for transfection into the CRC cells, and their effects on CRC cell lines were evaluated based on the conduction of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, colony formation assay, and flow cytometry assay. Eventually, the Luciferase reporter gene assay was carried out to judge if there existed a targeted relationship between ATB and miR‐200c. The results of Cox regression analyses suggested that overexpressed lncRNA ATB, underexpressed miR‐200c, poor tumor differentiation, lymph‐vascular invasion, and perineural invasion were symbolic of shortened survival of the patients with CRC (all P < .05). Besides, transfection of pcDNA3.1‐ATB and miR‐200c inhibitor could boost the viability and proliferation of Lovo and SW620 cell lines (all P < .05). Meanwhile, the expressions of p53 and p21 were also reduced under treatments of pcDNA3.1‐ATB and miR‐200c inhibitor (P < .05). In addition, CDK2 seemed to reverse the contribution of miR‐200c to intensifying viability and proliferation of Lovo and SW420 cell lines (P < .05). Furthermore, ATB might downregulate miR‐200c expression by targeting it (P < .05), and CDK2 was subjected to dual regulation of both ATB and miR‐200c (P < .05). In conclusion, the lncRNA ATB/miR‐200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC.

<p>LncRNA-ATB Promotes the Tumorigenesis of Ovarian Cancer via Targeting miR-204-3p</p>

“…30 In addition, lncRNA-ATB could promote the progression of colorectal cancer by regulating miR-200c/CDK2 axis. 31 These findings were similar to our previous research, indicating that lncRNA-ATB promoted the tumorigenesis of ovarian cancer via sponging miR-204-3p.…”

lncRNA‑ATB promotes stemness maintenance in colorectal cancer by regulating transcriptional activity of the β‑catenin pathway

“…Knockdown of ATB in endometrial cancer cells was found to impair cell viability by inducing caspase-3-related tumor apoptosis and G 1 /S arrest (27). In addition, ATB was responsible for the proliferation and apoptosis of CRC cells (18). The results demonstrated that ATB knockdown impaired stemness maintenance of CRC cells, indicated by the inhibition of colony formation and sphere formation, and colon tumor growth inhibition.…”

“…lncRNA activated by transforming growth factor-β (ATB) has been identified as a novel transforming growth factor-β (TGF-β)-induced lncRNA that stimulates cancer cell proliferation, metastasis, epithelial-mesenchymal transition (EMT) and angiogenesis in lung, bladder, breast and gastric cancer (14)(15)(16)(17). In CRC, ATB promoted cancer cell proliferation and was found to be a predictor of poor prognosis in patients (18,19). However, the regulatory role of ATB in the maintenance of CRC cell stemness remains unclear.…”

miR-200c /FUT4 axis prevents the migration, invasion and proliferation of colon cancer cells by downregulating Wnt/β-catenin pathway

“…As a member of miRNA family, miR-200 affects metastasis in some type of cancers. 9,10 In this study, the regulatory mechanism of miR-200c on colon cancer metastasis deserves was rstly evaluated. We found that the mRNA expression of miR-200c in Lovo and SW480 cells was remarkably lower than that in NCM460 cells, and the miR-200c overexpression treatment could inhibit proliferation of Lovo and SW480 cells.…”

“…8 Accumulating evidence suggests that miR-200 family is an epigenetic regulator of epithelialto-mesenchymal transition and involved in cancer progression. 9,10 Among them, there are many studies on miR-200c and colon cancer, and it has been shown that low expression of miR-200c is associated with poor prognosis of patients. [11][12][13] However, the regulation of colon cancer metastasis by miR-200c is a complex biological network.…”