My note on paper: A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer

Paper: A novel oncoprotein RNF43 functions in an autocrine manner in colorectal cancer
(doi:10.3892/ijo.25.5.1343)

Abstract:
1. Analyze expression profiles of 20 colorectal tumors by microarray - found genes upregulate in CRC - but look more detail on RNF43
2. northern blot reveals
- undetectable in normal tissue
- low expression in fetal kidney and lung
3. growth promoting effect in
- COS7
- NIH3T3
4. RNAi - limit the growth of colon cancer
5. Secretory protein and have the autocrine effect - can be used as novel diagnostic marker for CRC

CRC occurs from genetic alterations:

Tumor suppressor/Onco - APC, p53, beta-catenin and K-ras

Epigenetic affect - methylation, loss of imprinting, other unk

Gap for CRC:

1.Advance stage of CRC results in high mortality

2. Development of sensitivity and specific diagnostic biomarkers to detect early stage, developing more  effective and less harmful therapeutic drugs (to be able to design this kind of thing - requires the molecular mechanism of CRC)

RNF43 is frequently up-regulated in CRC, oncogenic activity, have essential role in cancer viability. 

Method:

Cell lines:

HEK293 (human embryonic kidney cell)

COS7 (African green monkey kidney fibroblast-like cell line)

NIH3T3

SW480, SNUC4 (human colon cancer)

HeLa (human cervical cancer)

In result:

1.11 colon cancer tissue compare with non-cancerous mucosae (microarray; 23,040 genes)

2. 51 genes highly expressed; interested in FLJ20315 (GI:NM_017763-RNF43)

3. RNF43 showed tumor/normal intensity ratio >2 (10 out of 11)

4. qPCR - found 15/18 colon tissues (more samples)

5. finding RNF43 (northern blot) in normal tissues

Adult - not detectable

Fetal - detect in Kidney and Lung

6. RNF43

- genomic region NT_010783

- chromosome band 17q23.2

- 11exons in 60kb of genomic region

- predicted RNF43 protein; 1-27 SP, 272-312 RING

- larger size of WB - suggest post-translational modification

- RNF43 is secretory protein

- RNF43 promotes the cell growth as autocrine manner (using the secretory protein to co-incubate with other cell lines and observe growth rate)

In discussion:

-mention the microdissection relates to highly expressed RNF43 should originate from cancer cell itself not mesenchymal cells

- highly expression in 

1.hepatocellular carcinomas

2. lung adenocarcinomas