<p>Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Cell Progression and Paclitaxel Resistance by Regulating miR-126-5p/ATAD2 Axis</p>

Abstract

Background: Long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) and microRNA-126-5p (miR-126-5p) were reported to be related to the development of colorectal carcinoma (CRC). However, the detailed mechanism of CRNDE and miR-126-5p is not fully understood. The purpose of this research was to explore their roles and molecular mechanism in CRC. Methods: Quantitative real-time polymerase chain reaction was performed to detect the transcription levels of genes. Paclitaxel (PTX) was used to analyze cell drug resistance. 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometry analysis were employed to assess cell proliferation and apoptosis, respectively. Furthermore, cell migratory and invasive abilities were measured using transwell assay. The interaction between miR-126-5p and CRNDE or ATPase family AAA domain-containing protein 2 (ATAD2) was predicted by online tool starbase and then confirmed using the dualluciferase reporter assay. Besides, Western blot assay was carried out to detect the levels of proteins. Results: CRNDE and ATAD2 expressions were upregulated and miR-126-5p expression was downregulated in CRC tissues and cells. CRNDE depletion repressed PTX resistance and the growth of CRC cells. Interestingly, we found that miR-126-5p was a target gene of CRNDE, and miR-126-5p directly targeted ATAD2. Furthermore, CRNDE affected CRC cell progression via modulation of miR-126-5p/ATAD2 axis in CRC cells. Conclusion: Our data suggested that CRNDE regulated CRC cell development and PTX resistance by modulating miR-126-5p/ATAD2 axis, providing the theoretical basis for the treatment of CRC patients.

Potential Role of miRNAs in the Acquisition of Chemoresistance in Neuroblastoma

“…Down-regulated in MYCN-amplified NB [22,29] and in chemoresistant NB [13] Down-regulated in cervical [30], breast [31,32] gastric [32,33], and lung [34] cancer, osteosarcoma [35], and mesothelioma [36] miR-19b 7.75 Up-regulated in chemoresistant NB [37] Down-regulated in breast [38] and colon [39] cancer and leukemia [40] miR-26b 47.87 Not evaluated Down-regulated in chemoresistant colorectal [41], gastric [42], laryngeal [43], and hepatocellular carcinoma [44,45] cancer and in glioma [46] [48], breast [49], and gastric cancer [50] miR-29c 9.27 Not evaluated Down-regulated in ovarian [51], endometrial [52], gastric [53], and small cell lung [54] cancer, glioma [55,56], and leukemia [57,58] miR-34c 7.49 Not evaluated Down-regulated in colon [59], gastric [60,61], and ovarian [62,63] cancer, and osteosarcoma [64] miR-126a 9.66 Not evaluated Down-regulated in colorectal [65] and breast cancer [66] and in renal cell carcinoma [67] miR-218 12.30…”

“…In detail, miR-27b and miR-16-1 expression levels were found to be reduced by 33.1 and 23.5 fold, respectively, and miR-218 expression was diminished by 9.09 fold, while miR-15a, miR-126, and miR-19b were down-regulated (slightly, but significantly) by 2.8, 2.7, and 1.73 fold, respectively. [59], gastric [60,61], and ovarian [62,63] cancer, and osteosarcoma [64] miR-126a 9.66 Not evaluated Down-regulated in colorectal [65] and breast cancer [66] and in renal cell carcinoma [67] miR-218 12.30 Up-regulated in MYCN-amplified and in metastatic NB [68][69][70] Down-regulated in glioma cells [71], colorectal [72], gallbladder [73], bladder [74], and lung cancer [75,76] miR-338 15.99 Down-regulated in resistant NB [77,78] Down-regulated in esophageal squamous carcinoma cells [79] miR-497 6.92…”

Long intergenic noncoding RNA 00665 promotes proliferation and inhibits apoptosis in colorectal cancer by regulating miR-126-5p

“…Further evidence showed that miR-126-5p is negatively correlated with LINC00665. It has been demonstrated that miR-126-5p plays a role as a tumor suppressor in many cancers [ 32 , 33 ], including CRC. Additionally, to confirm that LINC00665 competitively binds to miR-126-5p, related functional experiments were used.…”

Long non-coding RNA KCNQ1OT1 promotes cell viability and migration as well as inhibiting degradation of CHON-001 cells by regulating miR-126-5p/TRPS1 axis

“…Based on these results, we speculated that miR-126-5p may be a pathogenic miRNA existed in OA progression. On the other hand, miR-126-5p is revealed to act as the downstream targets of varied lncRNAs, such as lncRNA CRNDE [33], lncRNA HOTAIR [34], and lncRNA TMPO-AS1 [35].…”