Long noncoding RNA <em>CRNDE</em> functions as a competing endogenous RNA to promote metastasis and oxaliplatin resistance by sponging miR-136 in colorectal cancer

Abstract

Colorectal neoplasia differentially expressed (CRNDE) is a novel gene recognized as a long noncoding RNA (lncRNA) that is highly elevated in colorectal cancer and many other solid tumors but its functions on metastasis and oxaliplatin (OXA) resistance are unknown. In our study, we confirmed the upregulation of CRNDE in both primary specimens from colorectal cancer patients and colorectal cancer cell lines. Knockdown of CRNDE expression inhibited the migration and invasion potency of colorectal cancer cells with no effect on cell apoptosis. Overexpression of CRNDE promoted the migration and invasion potency of colorectal cancer cells. Furthermore, we found that CRNDE conferred chemoresistance in colorectal cancer cells. Knockdown of CRNDE with OXA treatment decreased cell viability and promoted DNA damage and cell apoptosis, while the overexpression of CRNDE with OXA treatment reduced DNA damage and cell apoptosis. Further in-depth mechanistic studies revealed that CRNDE functioned as a competing endogenous RNA for miR-136, led to the de-repression of its endogenous target, E2F transcription factor 1 (E2F1). Overall, our findings demonstrate that CRNDE functions as a competing endogenous RNA to promote metastasis and OXA resistance by sponging miR-136 in colorectal cancer.

Long non‐coding RNA CRNDE sponges miR‐384 to promote proliferation and metastasis of pancreatic cancer cells through upregulating IRS1

“…It has been reported that lncRNA CRNDE is upregulated in several kinds of cancers . In this research work, we initially detected the expression levels of CRNDE in 58 pairs of primary pancreatic cancer tissues as well as adjacent non‐tumour tissues.…”

“…It has been reported that lncRNA CRNDE is upregulated in several kinds of cancers. [14][15][16] In this research work, we initially detected the by coordinating and amplifying many signals in tumour cells. 35 Wang et al 36 showed that IRS1 expression was significantly boosted in both breast cancer cell lines and tissues, and overexpression of IRS1 could reverse miR-195-mediated repression of tumour cell proliferation; moreover, miR-195 inhibited tumour angiogenesis via IRS1.…”

“…17 For example, lncRNA CRNDE plays its role being a ceRNA for the promotion of metastasis through sponging miR-136 in colorectal cancer. 14 Increasing evidences have demonstrated that aberrant expression or dysfunction of miRNAs performs quintessential functions in the initiation and the progression of various cancers. [19][20][21] Nevertheless, there have been no reports dealing with the interaction between CRNDE and miRNA in pancreatic cancer as yet.…”

Non-coding RNA: It’s Not Junk

“…Liu and colleagues have a genome-scale systematic approach for inhibiting lncRNA expression in cancer cell lines and induced pluripotent stem cells (iPSCs) in order to determine functional outcomes. [13] They created a CRISPR-mediated interference library that enabled them to downregulate 16,401 different lncRNA loci in their cell models. Inhibition of 499 of the lncRNAs perturbed transcriptional networks and reduced the rate of cell growth.…”

Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways

“…For example, the effect of cisplatin on DNA formation is mainly the crosslinking between Pt-AG and Pt-GG chains, and crosslinking can also take place between the chains and DNA-protein, which can block DNA replication and transcription at the nucleic acid level, inhibit the division of tumor cells and induce apoptosis (11,12). The mechanisms of cisplatin resistance in tumor cells are as follows: i) Abnormal nucleotide excision repair system (13,14); ii) activation of the drug detoxification mechanism (15,16); iii) abnormal gene expression (17,18); iv) reduction in the movement of drugs into cancer cells and increased pump activity (19,20) and v) abnormal activation of cellular signaling pathways (21)(22)(23). Among these mechanisms, abnormal gene expression and cell signaling pathways have an important role in resistance to chemotherapy, and the selection of chemotherapeutics in colon cancer is becoming a research hotspot.…”