COLON CANCER / BASIC RESEARCH
 
KEYWORDS
TOPICS
ABSTRACT
Introduction:
This study aimed to investigate the effects of the lncRNA PCA3 in colon cancer and the associated mechanisms.

Material and methods:
Adjacent normal and cancer tissues were collected from colon cancer patients, and their PCA3 expression was measured by ISH and RT-qPCR assays. The correlations of PCA3 with clinical pathology and prognosis were also analysed. In addition, PCA3 and si-PCA3 were transfected into colon cancer cells (HT-29 and SW620). Moreover, cell proliferation, apoptosis, number of invading cells, and wound healing rate were determined by MTT, flow cytometry, Transwell, and wound healing assays. The relative protein expression was evaluated by western blotting.

Results:
Compared with that in normal tissues, PCA3 expression was significantly increased in colon cancer (p < 0.001). High PCA3 expression was correlated with malignant pathology and poor prognosis in patients. Compared with that in HCoEpic cells, PCA3 gene expression was significantly upregulated in SW480, HT-29, SW620, and HCT116 cells (all p < 0.01). With PCA3 transfection, cell proliferation increased, apoptosis decreased, and the number of invading cells and wound healing rate increased. In addition, RhoC, Bcl-2 and MMP-2 proteins increased, while Bax was suppressed. With the transfection of si-PCA3, which knocked down PCA3 expression, cell proliferation decreased, apoptosis increased, and the number of invading cells and wound healing rate decreased. Furthermore, RhoC, Bcl-2, and MMP-2 proteins decreased, while Bax increased.

Conclusions:
PCA3 is an oncogene in colon cancer. In vitro analysis indicates that knockdown of PCA3 suppresses the biological activities of colon cancer cells via the regulation of RhoC.
REFERENCES (28)
1.
Peng JS, Lad NL, Spangenthal EJ, Mattson DM, Nurkin SJ. Preoperative radiation as part of a multidisciplinary strategy for a medically inoperable patient with a bleeding colon cancer. BMJ Case Rep 2019; 12: pii: e229488.
 
2.
Turner ND, Lloyd SK. Association between red meat consumption and colon cancer: a systematic review of experimental results. Exp Biol Med 2017; 242: 813-39.
 
3.
Rajamanickam V, Yan T, Xu S, et al. Selective targeting of the TLR4 co-receptor, MD2, prevents colon cancer growth and lung metastasis. Int J Biol Sci 2020; 16: 1288-302.
 
4.
Yabushita S, Fukamachi K, Tanaka H, et al. Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas. Carcinogenesis 2013; 34: 1251-9.
 
5.
Gu C, Zou S, He C, et al. Long non-coding RNA CCAT1 promotes colorectal cancer cell migration, invasiveness and viability by upregulating VEGF via negative modulation of microRNA-218. Exp Ther Med 2020; 19: 2543-50.
 
6.
Xu G, Zhu H, Xu J, et al. Long non-coding RNA POU6F2-AS2 promotes cell proliferation and drug resistance in colon cancer by regulating miR-377/BRD4. J Cell Mol Med 2020; 24: 4136-49.
 
7.
Wang XY, Jian X, Sun BQ, Ge XS, Huang FJ, Chen YQ. LncRNA ROR1-AS1 promotes colon cancer cell proliferation by suppressing the expression of DUSP5/CDKN1A. Eur Rev Med Pharmacol Sci 2020; 24: 1116-25.
 
8.
Lemos AE, Ferreira LB, Batoreu NM, de Freitas PP, Bonamino MH, Gimba ER. PCA3 long noncoding RNA modulates the expression of key cancer-related genes in LNCaP prostate cancer cells. Tumour Biol 2016; 37: 11339-48.
 
9.
He JH, Li BX, Han ZP, et al. Snail-activated long non-coding RNA PCA3 up-regulates PRKD3 expression by miR-1261 sponging, thereby promotes invasion and migration of prostate cancer cells. Tumour Biol 2016; 37: 16163-76.
 
10.
Hanze J, Jakubowski P, Heers H, et al. Assessing blood platelets as RNA biomarker source for prostate cancer. Biomarkers 2016; 21: 653-9.
 
11.
Feibus AH, Sartor O, Moparty K, et al. Clinical use of PCA3 and TMPRSS2: ERG urinary biomarkers in African-American men undergoing prostate biopsy. J Urol 2016; 196: 1053-60.
 
12.
Zheng K, Dou Y, He L, et al. Improved sensitivity and specificity for prostate cancer diagnosis based on the urine PCA3/PSA ratio acquired by sequence specific RNA capture. Oncol Rep 2015; 34: 2439-44.
 
13.
Salameh A, Lee AK, Cardo-Vila M, et al. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proc Natl Acad Sci USA 2015; 112: 8403-8.
 
14.
Quek SI, Wong OM, Chen A, et al. Processing of voided urine for prostate cancer RNA biomarker analysis. Prostate 2015; 75: 1886-95.
 
15.
Donovan MJ, Noerholm M, Bentink S, et al. A molecular signature of PCA3 and ERG exosomal RNA from non-DRE urine is predictive of initial prostate biopsy result. Prostate Cancer Prostatic Dis 2015; 18: 370-5.
 
16.
He M, Cheng Y, Li W, et al. Vascular endothelial growth factor C promotes cervical cancer metastasis via up-regulation and activation of RhoA/ROCK-2/moesin cascade. BMC Cancer 2010; 10: 170.
 
17.
Matsuoka T, Yashiro M. Rho/Rock signaling in motility and metastasis of gastric cancer. World J Gastroenterol 2014; 20: 13756-66.
 
18.
Voorneveld PW, Kodach LL, Jacobs RJ, et al. Loss of SMAD4 alters BMP signaling to promote colorectal cancer cell metastasis via activating of Rho and ROCK. Gastroenterology 2014; 147: 196-208.e13.
 
19.
Brauer PR, Kim JH, Ochoa HJ, et al. Kruppel-like factor 4 mediates cellular migration and invasion by altering RhoA activity. Cell Commun Adhes 2018; 24: 1-10.
 
20.
Hoeppner LH, Sinha S, Wang Y, et al. RhoC maintains vascular homeostasis by regulating VEGF-induced signaling in endothelial cell. J Cell Sci 2015; 128: 3556-68.
 
21.
Liu BL, Sun KX, Zong ZH, Chen S, Zhao Y. MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC). Oncotarget 2016; 7: 6649-64.
 
22.
Zhao Y, Zheng HC, Chen S, Gou WF, Xiao LJ, Niu ZF. The role of RhoC in ovarian epithelial carcinoma: a marker for carcinogenesis, progression, prognosis, and target therapy. Gynecol Oncol 2013; 130: 570-8.
 
23.
Sharifi S, Barar J, Hejazi MS, Samadi N. Doxorubicin changes Bax /Bcl-xL ratio, caspase-8 and 9 in breast cancer cells. Adv Pharm Bull 2015; 5: 351-9.
 
24.
Vafaiyan Z, Gharaei R, Asadi J. The correlation between telomerase activity and Bax/Bcl- 2 ratio in valproic acid- treated MCF-7 breast cancer cell line. Iran J Basic Med Sci 2015; 18: 700-4.
 
25.
Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nat Rev Cancer 2014; 14: 430-9.
 
26.
Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep 2014; 15: 1243-53.
 
27.
Mahecha AM, Wang H. The influence of vascular endothelial growth factor: a and matrix metalloproteinaser-2 and -9 in angiogenesis, metastasis, and prognosis of endometrial cancer. Onco Targets Ther 2017; 10: 4617-24.
 
28.
Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A. Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol Rep 2009; 21: 1323-33.
 
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ISSN:1734-1922
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